Glioma
Conditions
Keywords
relapsed, lapatinib, Pazopanib, glioblastoma
Brief summary
This study is being conducted to characterize the safety/tolerability of pazopanib and lapatinib when administered in combination with enzyme-inducing anticonvulsants in patients with recurrent Grade III or IV malignant gliomas.
Detailed description
This study is being conducted to characterize the safety/tolerability of pazopanib and lapatinib when administered in combination with enzyme-inducing anticonvulsants in patients with recurrent Grade III or IV malignant gliomas.
Interventions
DRUGpazopanib
Pazopanib is a novel compound being developed for the treatment of various cancers.
DRUGlapatinib
Lapatinib is a novel compound being developed for the treatment of various cancers.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Phase I * Patients are on EIAC for a minimum of 15 days. Patients may be on more than one anti-convulsant (AC). At least one of the ACs must be an EIAC. * Patients with anaplastic astrocytoma, anaplastic oligodendroglioma, mixed anaplastic oligoastrocytoma, glioblastoma multiforme, or gliosarcoma at recurrence * Patients whose diagnostic pathology confirmed these pathologies will not need re-biopsy * Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to Grade III or IV malignant glioma Phase II * Patients must have histologically confirmed glioblastoma multiforme or gliosarcoma in first or second recurrence. * Patients may not have received more than two prior cytotoxic chemotherapy containing regimen. * Patients must not have received prior treatment with VEGFR, ErbB1, ErbB2 inhibitors including but not limited to PTK-787, Sorafenib, Sutent, Tarceva, Iressa, Erbitux, and Herceptin. Prior Avastin therapy is permitted provided three months has elapsed before Day 1, Treatment Period 1. * Tumor tissue must be analyzed for PTEN and epidermal growth factor receptor (EGFR) vIII prior to dosing. * Patients with prior low-grade glioma are eligible if histologic assessment demonstrates transformation to Grade IV malignant glioma. * Patients must not be on an EIAC. NOTE: Once the (optimally tolerated regimen) OTR in Phase I is determined and all patients in the expanded cohort have completed 1 treatment period then patients on EIAC may be enrolled in the Phase II component of the study. Phase I and II * Male or female, age at least 18 years of age. * Eastern Cooperative Oncology Group (ECOG) status 0 to 1 as per protocol. * Clinical lab results as per protocol * Has a left ventricular ejection fraction (LVEF) at least 50% based on echocardiogram (ECHO) or Multi Gated Aquisition (MUGA) or within the institutional normal range. * Adequate renal function * Creatinine clearance more than 50 mL/min as calculated by the Cockcroft-Gault formula as per protocol. * Urine Protein Creatinine (UPC) ratio of less than or equal to 1 as per protocol. * Able to swallow and retain oral medications. * A woman is eligible to enter and participate in the study if she is of: \- Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who: * Has had a hysterectomy, * Has had a bilateral oophorectomy (ovariectomy), * Has had a bilateral tubal ligation, * Is post-menopausal (total cessation of menses for at least 1 year) \- Childbearing potential, has a negative serum pregnancy test at screening, and agrees to use adequate contraception. Acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: * An intrauterine device (IUD) with a documented failure rate of less than 1% per year. * Vasectomized partner who is sterile prior to the female patient's entry and is the sole sexual partner for that female. * Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide). * A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study. * If sexually active, patients will continue the recommended contraceptive measures for the duration of the treatments and for 28 days following discontinuation of therapy. * Signed informed consent approved by the Institutional Review Board prior to patient entry.
Exclusion criteria
* Poorly controlled hypertension as per protocol. NOTE: Initiation or adjustment of BP medication is permitted prior to study entry provided that patient has two consecutive BP readings less than 140/90 mmHg each separated by a minimum of 24 hrs. These readings need to be collected prior to enrolment. * Concurrent severe and/or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive cardiac failure, poorly controlled hypertension, history of labile hypertension, history of poor compliance with antihypertensive regimen, chronic renal disease, or active uncontrolled infection) that could compromise participation in the study. * History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1, Treatment Period 1. * Has Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system as per protocol. * QTc prolongation defined as a corrected QT (QTc) interval greater than or equal to 470 milliseconds. * History of venous or arterial thrombosis within 3 months of Day 1, Treatment Period 1. * Current use of therapeutic warfarin. NOTE: both low molecular weight heparin and prophylactic low-dose warfarin are permitted; however, prothrombin time/partial thromboplastin time (PT/PTT) must meet above inclusion criteria. * Excessive risk of bleeding as defined by stroke within the prior 6 months, history of central nervous system (CNS) or intraocular bleed, or septic endocarditis. * Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative Grade 1 hemorrhage. * Active systemic bleeding, such as gastrointestinal bleeding or gross hematuria. * Female patients who are pregnant or breast feeding. * Acute or chronic liver disease (i.e., hepatitis, cirrhosis). * Patients who received investigational drugs less than 21days prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy. * Patients who received chemotherapy less than or equal to 21days prior (6 weeks for prior nitrosourea or mitomycin C) to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy. * Patients who received radiation therapy less than or equal to 12 weeks prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy as per protocol. * Patients who received biologic, immunotherapeutic or cytostatic agents less than or equal to 14 days prior to Day 1, Treatment Period 1, or who have not recovered from the toxic effects of such therapy. * Patient is less than 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention. Patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * Surgical resection of brain tumor or any other surgery less than or equal to 21 days prior to Day 1, Treatment Period 1, or who have not recovered from side effects of such a procedure. Patients who undergo stereotactic biopsy less than or equal to 14 days prior to Day 1 of Treatment Period 1, or who have not recovered from side effects of such a procedure. * Patients with any Grade of intraparenchymal CNS hemorrhage. Exceptions include Grade 1 intraparenchymal hemorrhage in the immediate post-operative period, or Grade 1 intraparenchymal hemorrhage that has been stable for at least 3 months. * Patients unwilling to or unable to comply with the protocol. * Any serious and/or unstable pre-existing medical, psychiatric, or other condition (including lab abnormalities) that could interfere with patient safety or obtaining informed consent. * History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Has any unresolved bowel obstruction or diarrhea. * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. * Is on any specifically prohibited medication or requires any of these medications during treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival at 6 Months | Date of the first dose of study drug to 6 months | Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting. |
| Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | Cycle 1 in Phase I (up to Day 28) | A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity. |
| Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) | OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w. |
| Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) | OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w. |
| Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878) | OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w. |
| Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) | Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury. |
| Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) | Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury. |
| Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II) | Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3 | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time) | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample. |
| Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time | Baseline to study completion (up to 878 days for Phase II) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine) | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3 | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells. |
| Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. |
| Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | Baseline to study completion (up to 844 days for Phase I) | Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC. | Completed during first cycle of treatment. | — |
| Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC. | Completed during first cycle of treatment. | — |
| Progression-free Survival | Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878) | Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. |
| Time to Disease Progression or Death Due to Any Cause | Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878) | — |
| Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2. | Completed during first cycle of treatment. | — |
Participant flow
Recruitment details
Phase I and Phase II had two separate participant populations. Enrollment in Phase II was not dependent on the number of participants completing Phase I.
Participants by arm
| Arm | Count |
|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg Starting dose of oral pazopanib of 200 milligrams (mg) once daily (OD) and oral lapatinib 1500 mg OD. The dose of pazopanib (200-800 mg) and lapatinib (500-1500 mg) in cohorts enrolled subsequent to the first dose cohort was determined by the toxicity profile of the combination therapy and the pharmacokinetic results from the prior cohort. | 34 |
| Phase II: Biomarker Positive All participants received pazopanib 400 mg twice daily (BID) and lapatinib 1000 mg OD. Biomarker-positive participants were those who expressed epithelial growth factor receptor vIII (EGFRvIII) and/or phosphate and tensin homolog (PTEN). | 19 |
| Phase II: Biomarker Negative All participants received pazopanib 400 mg OD and lapatinib 1000 mg OD. Biomarker-negative participants were those who did not express either EGFRvIII and/or PTEN. | 22 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Phase I: Dose Escalation | Adverse Event | 4 | 0 | 0 |
| Phase I: Dose Escalation | Death | 1 | 0 | 0 |
| Phase I: Dose Escalation | Lack of Efficacy | 25 | 0 | 0 |
| Phase I: Dose Escalation | Physician Decision | 1 | 0 | 0 |
| Phase I: Dose Escalation | Transition to Extension Phase | 3 | 0 | 0 |
| Phase II | Adverse Event | 0 | 1 | 1 |
| Phase II | Clinical Deterioration | 0 | 1 | 0 |
| Phase II | Death | 0 | 0 | 2 |
| Phase II | Disease Progression | 0 | 15 | 16 |
| Phase II | Enrolled in Rollover Study | 0 | 0 | 1 |
| Phase II | Sponsor Terminated Study | 0 | 0 | 1 |
| Phase II | Withdrawal by Subject | 0 | 2 | 1 |
Baseline characteristics
| Characteristic | Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Phase II: Biomarker Positive | Phase II: Biomarker Negative | Total |
|---|---|---|---|---|
| Age, Customized 20-29 years old | 1 participants | 0 participants | 2 participants | 3 participants |
| Age, Customized 30-39 years old | 8 participants | 0 participants | 3 participants | 11 participants |
| Age, Customized 40-49 years old | 11 participants | 6 participants | 6 participants | 23 participants |
| Age, Customized 50-59 years old | 10 participants | 5 participants | 8 participants | 23 participants |
| Age, Customized 60-69 years old | 3 participants | 7 participants | 2 participants | 12 participants |
| Age, Customized >=70 years old | 1 participants | 1 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized African American/African Heritage | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White/Caucasian/European Heritage | 34 participants | 19 participants | 21 participants | 74 participants |
| Sex: Female, Male Female | 11 Participants | 5 Participants | 5 Participants | 21 Participants |
| Sex: Female, Male Male | 23 Participants | 14 Participants | 17 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 33 / 34 | 18 / 19 | 22 / 22 |
| serious Total, serious adverse events | 15 / 34 | 6 / 19 | 8 / 22 |
Outcome results
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin | -5.9 grams per liter (g/L) | Standard Deviation 9.57 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Albumin | -6.7 grams per liter (g/L) | Standard Deviation 9.95 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase, n=19, 21 | 18.6 International Units per Liter (IU/L) | Standard Deviation 54.02 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase, n=19, 22 | 56.1 International Units per Liter (IU/L) | Standard Deviation 131.99 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase, n=19, 22 | 36.4 International Units per Liter (IU/L) | Standard Deviation 88.5 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase, n=18, 19 | 291.50 International Units per Liter (IU/L) | Standard Deviation 443.725 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase, n=18, 19 | 171.63 International Units per Liter (IU/L) | Standard Deviation 606.986 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase, n=19, 21 | 33.9 International Units per Liter (IU/L) | Standard Deviation 109.99 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase, n=19, 22 | 52.7 International Units per Liter (IU/L) | Standard Deviation 178.02 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase, n=19, 22 | 132.7 International Units per Liter (IU/L) | Standard Deviation 393.89 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase | Amylase | 22.72 Units per liter (U/L) | Standard Deviation 28.06 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase | Lipase | 131.4 Units per liter (U/L) | Standard Deviation 318.13 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase | Amylase | 20.05 Units per liter (U/L) | Standard Deviation 30.288 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Amylase and Lipase | Lipase | 120.5 Units per liter (U/L) | Standard Deviation 163.51 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium, n=19, 21 | 0.17 millimoles per liter (mmol/l) | Standard Deviation 0.471 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium, n=19, 21 | 1.7 millimoles per liter (mmol/l) | Standard Deviation 2.96 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose, n=19, 21 | 0.082 millimoles per liter (mmol/l) | Standard Deviation 4.1342 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea, n=19, 21 | 0.770 millimoles per liter (mmol/l) | Standard Deviation 1.684 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium, n=19, 19 | 0.022 millimoles per liter (mmol/l) | Standard Deviation 0.0676 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus, n=19, 20 | 0.090 millimoles per liter (mmol/l) | Standard Deviation 0.2352 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium, n=19, 21 | 0.004 millimoles per liter (mmol/l) | Standard Deviation 0.1257 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus, n=19, 20 | 0.076 millimoles per liter (mmol/l) | Standard Deviation 0.2048 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium, n=19, 21 | 0.019 millimoles per liter (mmol/l) | Standard Deviation 0.0952 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose, n=19, 21 | 1.850 millimoles per liter (mmol/l) | Standard Deviation 2.718 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium, n=19, 21 | 0.30 millimoles per liter (mmol/l) | Standard Deviation 0.264 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium, n=19, 19 | 0.040 millimoles per liter (mmol/l) | Standard Deviation 0.0853 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium, n=19, 21 | 1.3 millimoles per liter (mmol/l) | Standard Deviation 1.85 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea, n=19, 21 | 1.071 millimoles per liter (mmol/l) | Standard Deviation 2.1736 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit | -0.016 percent | Standard Deviation 0.032 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Hematocrit | -0.027 percent | Standard Deviation 0.0452 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin | -4.6 grams per liter (g/L) | Standard Deviation 11.25 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Hemoglobin | -8.0 grams per liter (g/L) | Standard Deviation 16.75 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time) | 0.030 ratio | Standard Deviation 0.0663 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for International Normalized Ratio (Prothrombin Time) | 0.042 ratio | Standard Deviation 0.1094 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=16, 19 | -0.26 giga (10^9) per liter (GI/L) | Standard Deviation 0.556 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=16, 18 | -2.87 giga (10^9) per liter (GI/L) | Standard Deviation 3.021 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=19, 22 | -58.7 giga (10^9) per liter (GI/L) | Standard Deviation 53.98 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cells, n=19, 22 | -2.63 giga (10^9) per liter (GI/L) | Standard Deviation 2.934 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cells, n=19, 22 | -4.06 giga (10^9) per liter (GI/L) | Standard Deviation 6.026 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=16, 19 | -0.21 giga (10^9) per liter (GI/L) | Standard Deviation 0.573 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=19, 22 | -55.7 giga (10^9) per liter (GI/L) | Standard Deviation 59.79 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=16, 18 | -4.72 giga (10^9) per liter (GI/L) | Standard Deviation 5.067 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 2.10 seconds (sec) | Standard Deviation 1.985 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.0 seconds (sec) | Standard Deviation 0.57 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 2.62 seconds (sec) | Standard Deviation 3.175 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.2 seconds (sec) | Standard Deviation 1.19 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone | 1.37 milliunits per liter (mU/L) | Standard Deviation 2.106 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroid Stimulating Hormone | 2.59 milliunits per liter (mU/L) | Standard Deviation 4.377 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) | Thyroxine, n=16, 13 | -8.052 picomoles per liter (pmol/l) | Standard Deviation 30.2175 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) | Free T3, n=4, 4 | 0.420 picomoles per liter (pmol/l) | Standard Deviation 0.501 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) | Thyroxine, n=16, 13 | 10.806 picomoles per liter (pmol/l) | Standard Deviation 40.5626 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Thyroxine and Free T3 (Triiodothyronine) | Free T3, n=4, 4 | -2.442 picomoles per liter (pmol/l) | Standard Deviation 2.3525 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine | Total bilirubin | 6.174 micromoles per liter (µmol/l) | Standard Deviation 7.2714 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine | Creatinine | 6.93 micromoles per liter (µmol/l) | Standard Deviation 10.444 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine | Total bilirubin | 23.562 micromoles per liter (µmol/l) | Standard Deviation 71.1671 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total Bilirubin and Creatinine | Creatinine | 9.59 micromoles per liter (µmol/l) | Standard Deviation 14.852 |
Primary
Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 878 days for Phase II)
Population: All-treated Population for Phase II. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3 | -0.181 nanomoles per liter (nmol/l) | Standard Deviation 0.6521 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase II of the Study for Total T3 | -0.104 nanomoles per liter (nmol/l) | Standard Deviation 0.3516 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -4.25 grams per liter (g/L) | Standard Deviation 4.573 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -6.17 grams per liter (g/L) | Standard Deviation 5.707 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -3.80 grams per liter (g/L) | Standard Deviation 1.924 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -5.17 grams per liter (g/L) | Standard Deviation 3.545 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -13.66 grams per liter (g/L) | Standard Deviation 16.959 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Albumin | -7.17 grams per liter (g/L) | Standard Deviation 4.215 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 9.8 International Units per Liter (IU/L) | Standard Deviation 11.47 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 36.8 International Units per Liter (IU/L) | Standard Deviation 66.35 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 15.0 International Units per Liter (IU/L) | Standard Deviation 31.72 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 148.0 International Units per Liter (IU/L) | Standard Deviation 96.42 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 127.0 International Units per Liter (IU/L) | Standard Deviation 144.6 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 49.3 International Units per Liter (IU/L) | Standard Deviation 71.63 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 22.8 International Units per Liter (IU/L) | Standard Deviation 39.55 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 139.5 International Units per Liter (IU/L) | Standard Deviation 204.81 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 13.8 International Units per Liter (IU/L) | Standard Deviation 15.71 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 47.0 International Units per Liter (IU/L) | Standard Deviation 48.09 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 46.0 International Units per Liter (IU/L) | Standard Deviation 35.86 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 31.2 International Units per Liter (IU/L) | Standard Deviation 53.6 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 15.8 International Units per Liter (IU/L) | Standard Deviation 22.66 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 321.2 International Units per Liter (IU/L) | Standard Deviation 534.42 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 8.8 International Units per Liter (IU/L) | Standard Deviation 7.03 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 33.2 International Units per Liter (IU/L) | Standard Deviation 25.25 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 22.0 International Units per Liter (IU/L) | Standard Deviation 28.54 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 4.8 International Units per Liter (IU/L) | Standard Deviation 7.19 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 124.7 International Units per Liter (IU/L) | Standard Deviation 136.46 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 13.5 International Units per Liter (IU/L) | Standard Deviation 16.2 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alkaline phosphatase | 22.0 International Units per Liter (IU/L) | Standard Deviation 47.15 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Aspartate aminotransferase | 19.3 International Units per Liter (IU/L) | Standard Deviation 18.47 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Lactate dehydrogenase | 116.8 International Units per Liter (IU/L) | Standard Deviation 59.26 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Alkaline Phosphatase, Alanine Aminotransferase, Aspartate Aminotransferase, and Lactate Dehydrogenase | Alanine aminotransferase | 47.7 International Units per Liter (IU/L) | Standard Deviation 56.43 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 24.3 Units per liter (U/L) | Standard Deviation 36.42 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 147.0 Units per liter (U/L) | Standard Deviation 292.02 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 24.4 Units per liter (U/L) | Standard Deviation 17.04 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 23.3 Units per liter (U/L) | Standard Deviation 44.98 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 27.3 Units per liter (U/L) | Standard Deviation 66.4 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 33.0 Units per liter (U/L) | Standard Deviation 56.79 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 31.0 Units per liter (U/L) | Standard Deviation 38.96 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 151.8 Units per liter (U/L) | Standard Deviation 230.63 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 44.4 Units per liter (U/L) | Standard Deviation 52.52 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 67.3 Units per liter (U/L) | Standard Deviation 101.83 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Amylase | 23.3 Units per liter (U/L) | Standard Deviation 39.38 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Amylase and Lipase | Lipase | 7.8 Units per liter (U/L) | Standard Deviation 21.09 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | 0.069 millimoles per liter (mmol/l) | Standard Deviation 0.0237 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.075 millimoles per liter (mmol/l) | Standard Deviation 0.4992 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | -0.062 millimoles per liter (mmol/l) | Standard Deviation 0.025 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.02 millimoles per liter (mmol/l) | Standard Deviation 0.168 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 0.56 millimoles per liter (mmol/l) | Standard Deviation 1.385 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 1.9 millimoles per liter (mmol/l) | Standard Deviation 0.18 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | -1.000 millimoles per liter (mmol/l) | Standard Deviation 1.8257 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 3.35 millimoles per liter (mmol/l) | Standard Deviation 6.653 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.400 millimoles per liter (mmol/l) | Standard Deviation 0.3033 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | -0.045 millimoles per liter (mmol/l) | Standard Deviation 0.1173 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | 0.500 millimoles per liter (mmol/l) | Standard Deviation 2.0736 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.11 millimoles per liter (mmol/l) | Standard Deviation 0.186 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | -0.019 millimoles per liter (mmol/l) | Standard Deviation 0.0573 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 0.6 millimoles per liter (mmol/l) | Standard Deviation 1.18 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | 1.800 millimoles per liter (mmol/l) | Standard Deviation 1.6432 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | 0.036 millimoles per liter (mmol/l) | Standard Deviation 0.0572 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 1.20 millimoles per liter (mmol/l) | Standard Deviation 1.114 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | 0.058 millimoles per liter (mmol/l) | Standard Deviation 0.0463 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.420 millimoles per liter (mmol/l) | Standard Deviation 0.3033 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 0.8 millimoles per liter (mmol/l) | Standard Deviation 1.74 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.41 millimoles per liter (mmol/l) | Standard Deviation 0.553 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | 1.333 millimoles per liter (mmol/l) | Standard Deviation 2.0656 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | 0.051 millimoles per liter (mmol/l) | Standard Deviation 0.051 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.500 millimoles per liter (mmol/l) | Standard Deviation 0.2608 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | 0.061 millimoles per liter (mmol/l) | Standard Deviation 0.0874 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 1.02 millimoles per liter (mmol/l) | Standard Deviation 2.654 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 1.1 millimoles per liter (mmol/l) | Standard Deviation 1.27 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.16 millimoles per liter (mmol/l) | Standard Deviation 0.164 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 0.9 millimoles per liter (mmol/l) | Standard Deviation 1.2 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | 0.047 millimoles per liter (mmol/l) | Standard Deviation 0.1155 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 1.55 millimoles per liter (mmol/l) | Standard Deviation 0.589 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | 1.500 millimoles per liter (mmol/l) | Standard Deviation 4.5497 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | 0.043 millimoles per liter (mmol/l) | Standard Deviation 0.0615 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.600 millimoles per liter (mmol/l) | Standard Deviation 0.5967 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.01 millimoles per liter (mmol/l) | Standard Deviation 0.129 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Calcium | -0.014 millimoles per liter (mmol/l) | Standard Deviation 0.1166 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Magnesium | 0.056 millimoles per liter (mmol/l) | Standard Deviation 0.092 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Potassium | 0.183 millimoles per liter (mmol/l) | Standard Deviation 0.2229 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Sodium | 0.000 millimoles per liter (mmol/l) | Standard Deviation 0.6325 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Inorganic phosphorus | 0.25 millimoles per liter (mmol/l) | Standard Deviation 0.185 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Urea | 1.7 millimoles per liter (mmol/l) | Standard Deviation 1.72 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Calcium, Glucose, Potassium, Magnesium, Inorganic Phosphorus, Sodium, and Urea | Glucose | 0.65 millimoles per liter (mmol/l) | Standard Deviation 0.934 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline. For some arms, data were not collected for either baseline or post-baseline assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine) | -0.07 picomoles per liter (pmol/l) | Standard Deviation 0.222 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Free T3 (Triiodothyronine) | -0.94 picomoles per liter (pmol/l) | Standard Deviation 1.291 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. The hematocrit is the proportion of blood volume that is occupied by red blood cells.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | -0.02 percent | Standard Deviation 0.034 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | -0.02 percent | Standard Deviation 0.029 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | -0.02 percent | Standard Deviation 0.023 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | 0.00 percent | Standard Deviation 0.027 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | -0.09 percent | Standard Deviation 0.103 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hematocrit | 0.01 percent | Standard Deviation 0.024 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -7.25 grams per Liter (g/L) | Standard Deviation 14.975 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -7.83 grams per Liter (g/L) | Standard Deviation 12.999 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -4.80 grams per Liter (g/L) | Standard Deviation 9.834 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -3.33 grams per Liter (g/L) | Standard Deviation 13.095 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -16.17 grams per Liter (g/L) | Standard Deviation 9.867 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Hemoglobin | -21.02 grams per Liter (g/L) | Standard Deviation 59.642 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time)
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Prothrombin time is a measure of the extrinsic pathway of coagulation that is used to determine the clotting tendency of blood. The International Normalized Ratio is the ratio of a patient's prothrombin time to a normal (control) sample.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phases I and II. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | 0.077 ratio | Standard Deviation 0.0866 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | -0.023 ratio | Standard Deviation 0.0638 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | 0.056 ratio | Standard Deviation 0.0472 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | 0.000 ratio | Standard Deviation 0.1097 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | 0.015 ratio | Standard Deviation 0.0764 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for International Normalized Ratio (Prothrombin Time) | 0.006 ratio | Standard Deviation 0.0134 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline. Partial thromboplastin time is a performance indicator detecting abnormalities in blood clotting.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 1.10 seconds (sec) | Standard Deviation 1.299 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.38 seconds (sec) | Standard Deviation 0.532 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 2.88 seconds (sec) | Standard Deviation 1.986 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.47 seconds (sec) | Standard Deviation 0.94 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 2.62 seconds (sec) | Standard Deviation 5.545 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.64 seconds (sec) | Standard Deviation 0.981 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | -0.38 seconds (sec) | Standard Deviation 6.122 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | -0.02 seconds (sec) | Standard Deviation 0.796 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 2.18 seconds (sec) | Standard Deviation 2.082 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 1.07 seconds (sec) | Standard Deviation 1.722 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Partial thromboplastin time | 1.00 seconds (sec) | Standard Deviation 1.093 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Partial Thromboplastin Time and Prothrombin Time | Prothrombin time | 0.56 seconds (sec) | Standard Deviation 0.885 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | -0.5068 milliunits per liter (mU/L) | Standard Deviation 1.99588 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | 0.1900 milliunits per liter (mU/L) | Standard Deviation 0.38931 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | 0.6543 milliunits per liter (mU/L) | Standard Deviation 0.73309 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | 0.6660 milliunits per liter (mU/L) | Standard Deviation 0.70497 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | 0.6080 milliunits per liter (mU/L) | Standard Deviation 11.10117 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroid Stimulating Hormone | 2.2940 milliunits per liter (mU/L) | Standard Deviation 1.25335 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | -0.740 picomoles per liter (pmol/l) | Standard Deviation 2.8496 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | -1.498 picomoles per liter (pmol/l) | Standard Deviation 1.8681 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | 1.105 picomoles per liter (pmol/l) | Standard Deviation 3.6173 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | 1.879 picomoles per liter (pmol/l) | Standard Deviation 2.8191 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | 0.377 picomoles per liter (pmol/l) | Standard Deviation 3.9731 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Thyroxine | -0.781 picomoles per liter (pmol/l) | Standard Deviation 1.004 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | -0.000 micromoles per liter (µmol/l) | Standard Deviation 4.6307 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 4.420 micromoles per liter (µmol/l) | Standard Deviation 15.3113 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | 2.613 micromoles per liter (µmol/l) | Standard Deviation 2.5162 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 8.367 micromoles per liter (µmol/l) | Standard Deviation 11.3656 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | 3.368 micromoles per liter (µmol/l) | Standard Deviation 2.152 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 7.336 micromoles per liter (µmol/l) | Standard Deviation 6.6049 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | 6.130 micromoles per liter (µmol/l) | Standard Deviation 6.0799 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 6.893 micromoles per liter (µmol/l) | Standard Deviation 6.6297 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | 4.135 micromoles per liter (µmol/l) | Standard Deviation 3.8089 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 9.727 micromoles per liter (µmol/l) | Standard Deviation 9.7448 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Total bilirubin | 6.398 micromoles per liter (µmol/l) | Standard Deviation 3.8952 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total Bilirubin and Creatinine | Creatinine | 12.005 micromoles per liter (µmol/l) | Standard Deviation 19.3179 |
Primary
Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided chemistry measurements at both baseline and post-baseline. For some arms, data were not collected for either baseline or post-baseline assessments.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3 | -0.071 nanomoles per liter (nmol/l) | Standard Deviation 0.1113 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3 | 0.214 nanomoles per liter (nmol/l) | Standard Deviation 0.2851 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in Phase I of the Study for Total T3 | 0.004 nanomoles per liter (nmol/l) | Standard Deviation 0.0028 |
Primary
Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count
Change from baseline is calculated as the maximum changed value in the study minus the value at Baseline.
Time frame: Baseline to study completion (up to 844 days for Phase I)
Population: All-treated Population for Phase I. Data are presented for only those participants who provided hematology measurements at both baseline and post-baseline.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -12.3 giga (10^9) per liter (GI/L) | Standard Deviation 30.08 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -0.845 giga (10^9) per liter (GI/L) | Standard Deviation 1.0849 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.377 giga (10^9) per liter (GI/L) | Standard Deviation 0.4611 |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -0.693 giga (10^9) per liter (GI/L) | Standard Deviation 1.0775 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.120 giga (10^9) per liter (GI/L) | Standard Deviation 0.4291 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -2.933 giga (10^9) per liter (GI/L) | Standard Deviation 3.6335 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -3.000 giga (10^9) per liter (GI/L) | Standard Deviation 3.2727 |
| Phase II: Biomarker Positive | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -74.7 giga (10^9) per liter (GI/L) | Standard Deviation 74.18 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -1.950 giga (10^9) per liter (GI/L) | Standard Deviation 2.1249 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.153 giga (10^9) per liter (GI/L) | Standard Deviation 0.3083 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -1.370 giga (10^9) per liter (GI/L) | Standard Deviation 1.5036 |
| Phase II: Biomarker Negative | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -65.4 giga (10^9) per liter (GI/L) | Standard Deviation 32.65 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -0.850 giga (10^9) per liter (GI/L) | Standard Deviation 0.9072 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.032 giga (10^9) per liter (GI/L) | Standard Deviation 0.2807 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -25.3 giga (10^9) per liter (GI/L) | Standard Deviation 40 |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -0.595 giga (10^9) per liter (GI/L) | Standard Deviation 0.8783 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -1.723 giga (10^9) per liter (GI/L) | Standard Deviation 1.732 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.218 giga (10^9) per liter (GI/L) | Standard Deviation 0.2316 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -35.5 giga (10^9) per liter (GI/L) | Standard Deviation 54.72 |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -1.717 giga (10^9) per liter (GI/L) | Standard Deviation 2.2355 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | White blood cell count, n=4, 6, 5, 6, 6, 6 | -0.850 giga (10^9) per liter (GI/L) | Standard Deviation 2.4468 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Lymphocytes, n=3, 6, 4, 6, 6, 6 | -0.250 giga (10^9) per liter (GI/L) | Standard Deviation 0.3017 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Platelet count, n=4, 6, 5, 6, 6, 6 | -61.8 giga (10^9) per liter (GI/L) | Standard Deviation 32.17 |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Mean Change From Baseline to Maximum Value in the Study for Lymphocytes, Neutrophils, Platelet Count, and White Blood Count | Total Neutrophils, n=3, 6, 4, 6, 6, 6 | -0.617 giga (10^9) per liter (GI/L) | Standard Deviation 2.7154 |
Primary
Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose
A dose-limiting toxicity (DLT) is defined as predefined adverse events or events that prevented participants from receiving 75% of their scheduled doses or from starting their next treatment period. The dose at which no more than 1 out of 6 participants experiences a DLT is defined as the optimally tolerated regimen. The OTR is important because it determines the highest dose combination that can be given without significant toxicity.
Time frame: Cycle 1 in Phase I (up to Day 28)
Population: All-treated Population for Phase I
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 0 participants |
| Phase II: Biomarker Positive | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 1 participants |
| Phase II: Biomarker Negative | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 1 participants |
| Phase I: Pazopanib 800 mg/Lapatinib 750 mg | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 1 participants |
| Phase I: Pazopanib 800 mg/Lapatinib 1000 mg | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 1 participants |
| Phase I: Pazopanib 600 mg/Lapatinib 1000 mg | Number of Participants Experiencing a Dose-limiting Toxicity at the Indicated Dose | 1 participants |
Primary
Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Population: All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg | 1 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg | 23 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg | 9 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg | 1 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg | 13 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg | 4 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, >=110 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 90-<110 mmHg | 2 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 50-<90 mmHg | 9 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 90-<110 mmHg; shift to post-BL, 50-<90 mmHg | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Diastolic Blood Pressure | BL, 50-<90 mmHg; shift to post-BL, 90-<110 mmHg | 10 participants |
Primary
Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. bpm, beats per minute.
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Population: All-treated Population for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 101-120 bpm | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, >120 bpm; shift to post-BL, 44-100 bpm | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 44-100 bpm | 31 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, 101-120 bpm | 2 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, missing; shift to post-BL, 44-100 bpm | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, >120 bpm | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, missing; shift to post-BL, 44-100 bpm | 1 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 44-100 bpm | 14 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, >120 bpm | 1 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 101-120 bpm | 3 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, 101-120 bpm | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, >120 bpm; shift to post-BL, 44-100 bpm | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, >120 bpm; shift to post-BL, 44-100 bpm | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, 101-120 bpm | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 101-120 bpm; shift to post-BL, >120 bpm | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 101-120 bpm | 2 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, missing; shift to post-BL, 44-100 bpm | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Heart Rate | BL, 44-100 bpm; shift to post-BL, 44-100 bpm | 19 participants |
Primary
Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure
Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline (BL) values to investigate what changes occurred. mmHg, millimeters of mercury.
Time frame: Baseline to study completion (up to 844 days for Phase I, up to 878 days for Phase II)
Population: All-treated Population (all participants who were given any dose of study medication) for Phases I and II. One participant withdrew in Phase I due to death; change from baseline was not calculated for this participant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg | 12 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg | 21 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg | 1 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg | 12 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg | 3 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg | 2 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg | 0 participants |
| Phase II: Biomarker Positive | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 140-<170 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 140-<170 mmHg | 8 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, >=170 mmHg; shift to post-BL, 140-<170 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, >=170 mmHg | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 140-<170 mmHg; shift to post-BL, 90-<140 mmHg | 0 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, >=170 mmHg | 1 participants |
| Phase II: Biomarker Negative | Number of Participants With the Indicated Change From Baseline to Study Completion in Systolic Blood Pressure | BL, 90-<140 mmHg; shift to post-BL, 90-<140 mmgHg | 11 participants |
Primary
Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Population: All-treated Population in Phase II who also had a response assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Partial response | 1 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Progressive disease, <8 weeks | 7 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Stable disease, >=8 weeks | 7 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Progressive disease | 4 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Complete response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Progressive disease | 6 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Complete response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Partial response | 2 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Stable disease, >=8 weeks | 6 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based GlaxoSmithKline's Evaluation | Progressive disease, <8 weeks | 8 participants |
Primary
Overall Response (OR) in Phase II Based on an Independent Radiologist's Review
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Population: All-treated Population for Phase II who also had a response assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Complete response | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Partial response | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Stable disease, >=8 weeks | 5 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Progressive disease, <8 weeks | 5 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Progressive disease | 4 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Unconfirmed partial response | 4 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Progressive disease | 6 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Complete response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Progressive disease, <8 weeks | 8 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Partial response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Unconfirmed partial response | 4 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on an Independent Radiologist's Review | Stable disease, >=8 weeks | 4 participants |
Primary
Overall Response (OR) in Phase II Based on the Investigator-assigned Response
OR is the number of participants whose response was classified as a complete response or partial response (disappearance of enhancing tumor (ET) or reduction of ET by \>=50%, respectively, on consecutive scans \[CS\] \>=1 month (m) apart, off steroids, and neurologically stable/improved), progressive disease (increase of ET of \>=25% on CS \>=1 m apart or neurologically worse, and steroids stable/increased), or stable disease (all other situations) per MacDonald criteria. Participants were evaluated with magnetic resonance imaging. Baseline and the 4- and 8-w assessments are categorized as \<8 w.
Time frame: Date of first dose of study drug to date of documented and confirmed progression, or to date of death due to any cause (assessed at baseline, 4 and 8 weeks, and every 8 weeks thereafter until study withdrawal; up to Day 878)
Population: All-treated Population for Phase II who also had a response assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Partial response | 1 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Progressive disease, <8 weeks | 7 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Stable disease, >=8 weeks | 7 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Progressive disease | 4 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Complete response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Progressive disease | 5 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Complete response | 0 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Partial response | 1 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Stable disease, >=8 weeks | 7 participants |
| Phase II: Biomarker Positive | Overall Response (OR) in Phase II Based on the Investigator-assigned Response | Progressive disease, <8 weeks | 9 participants |
Primary
Progression-free Survival at 6 Months
Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used. The participants who are still alive and whose follow-up extends to at least 6 months are considered At Risk.
Time frame: Date of the first dose of study drug to 6 months
Population: All-treated Population for Phase II
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival at 6 Months | Disease progression at or prior to 6 months | 15 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival at 6 Months | Death at or prior to 6 months | 0 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival at 6 Months | Censored at or prior to 6 months | 4 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival at 6 Months | At risk beyond 6 months | 0 participants |
| Phase II: Biomarker Positive | Progression-free Survival at 6 Months | At risk beyond 6 months | 3 participants |
| Phase II: Biomarker Positive | Progression-free Survival at 6 Months | Disease progression at or prior to 6 months | 16 participants |
| Phase II: Biomarker Positive | Progression-free Survival at 6 Months | Censored at or prior to 6 months | 1 participants |
| Phase II: Biomarker Positive | Progression-free Survival at 6 Months | Death at or prior to 6 months | 2 participants |
Secondary
Phase II: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, Tmax, and C24 of Pazopanib and Lapatinib, as Appropriate, When Administered Together in Combination With Non-EIAC.
Time frame: Completed during first cycle of treatment.
Secondary
Phase II: Plasma Concentrations of the Circulating Biomarkers VEGF, sVEGFR-1, and sVEGFR-2.
Time frame: Completed during first cycle of treatment.
Secondary
Phase I: Pharmacokinetic Parameters Including AUC(0-24), [AUC(0-12) for Patients on Twice Daily Administration], Cmax, the Time to Maximum Observed Concentration (Tmax) and C24 of Pazopanib and Lapatinib When Administered in Combination With EIAC.
Time frame: Completed during first cycle of treatment.
Secondary
Progression-free Survival
Progression-free survival (PFS) analysis was performed on all participants. PFS is presented as the number of participants experiencing disease progression or death due to any cause. Participants who are alive and have not progressed at the time of analysis are considered censored, and the date associated with the last visit with disease assessment will be used.
Time frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
Population: All-treated Population for Phase II
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival | Censored | 4 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival | Disease progression | 15 participants |
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Progression-free Survival | Death | 0 participants |
| Phase II: Biomarker Positive | Progression-free Survival | Disease progression | 18 participants |
| Phase II: Biomarker Positive | Progression-free Survival | Death | 2 participants |
| Phase II: Biomarker Positive | Progression-free Survival | Censored | 2 participants |
Secondary
Time to Disease Progression or Death Due to Any Cause
Time frame: Date of the first dose of study drug to the date of documented and confirmed progression by Mac Donald criteria, or to date of death due to any cause (up to Day 878)
Population: All-treated Population for Phase II
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase I: Pazopanib 200-800 mg/Lapatinib 500-1500 mg | Time to Disease Progression or Death Due to Any Cause | 62 days |
| Phase II: Biomarker Positive | Time to Disease Progression or Death Due to Any Cause | 56 days |