Epithelioid Mesothelioma, Pleural Malignant Mesothelioma, Recurrent Malignant Mesothelioma, Sarcomatoid Mesothelioma
Conditions
Brief summary
This randomized phase I/II trial is studying the side effects and best dose of cediranib maleate when given together with pemetrexed disodium and cisplatin and to see how well it works in treating patients with malignant pleural mesothelioma. Drugs used in chemotherapy, pemetrexed disodium and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving pemetrexed disodium and cisplatin together with cediranib maleate may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of cediranib maleate (cediranib) in combination with cisplatin and pemetrexed disodium (pemetrexed). (Phase I) II. To assess the safety and toxicity of the regimen. (Phase I) III. To assess whether cisplatin/pemetrexed plus cediranib as compared to cisplatin/pemetrexed plus placebo improves progression-free survival in patients with malignant pleural mesothelioma. (Phase II) IV. To compare overall survival in patients treated with cisplatin/pemetrexed plus cediranib to those treated with cisplatin/pemetrexed plus placebo. (Phase II) V. To assess the safety and toxicity profile of the regimen. (Phase II) VI. To assess response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in the subset of patients with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. (Phase II) VII. To assess response rate and disease control rate using modified RECIST criteria for pleural tumors in the subset of patients with measurable disease by modified RECIST criteria for pleural tumors. (Phase II) VIII. To assess the rate of agreement between local and central pathology review of mesothelioma and its histologic subtypes. (Phase II) IX. To collect specimens for banking for use in future research studies. (Phase II) OUTLINE: This is a phase I dose-escalation study of cediranib maleate followed by a phase II study. PHASE I (CLOSED): Patients receive pemetrexed disodium intravenously (IV) over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. PHASE II: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive pemetrexed disodium and cisplatin as in arm I and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years and then at 3 years.
Interventions
DRUGCediranib Maleate
Given orally
DRUGCisplatin
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPemetrexed Disodium
Given IV
OTHERPlacebo Administration
Given orally
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient must have histologically or cytologically confirmed diagnosis of malignant pleural mesothelioma; surgical resection must not be planned * Patients must have measurable or non-measurable disease by both RECIST and modified RECIST criteria for pleural tumors as documented by computed tomography (CT) scan; examinations for assessment of measurable disease must have been completed within 28 days prior to registration; examinations for assessment of non-measurable disease must have been performed within 42 days prior to registration; all disease must be assessed and documented on the RECIST 1.1 and Modified RECIST Baseline Tumor Assessment Form * Patients must not have received any prior systemic therapy (chemotherapy or other biologic therapy) for their unresectable malignant pleural mesothelioma; prior systemic chemotherapy or biologic therapy is allowed as neoadjuvant or adjuvant treatment, disease has now recurred, and all systemic treatment was completed \> 6 months prior registration; prior therapy must not have included cediranib * Patients may have received prior surgery (e.g., pleurectomy, pleurodeisis) provided at least 28 days have elapsed since surgery (thoracic or other major surgeries) and patients have recovered from all associated toxicities at the time of registration; there must be no anticipated need for major surgical procedures during protocol treatment * Patients may have received prior radiation therapy provided at least 28 days have elapsed since the last treatment and patients have recovered from all associated toxicities at the time of registration * Institutions must seek additional patient consent for the banking and future use of specimens * Patient must have Zubrod performance status 0-2 * Absolute neutrophil count \>= 1,500 mcl * Platelets \>= 100,000/ml * Hemoglobin \>= 9.0 g/dl (may be reached by transfusion) * Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) * Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x ULN (if liver metastases are present, SGOT or SGPT must be =\< 5.0 x IULN) * Serum creatinine =\< 1.5 x IULN * Calculated creatinine clearance \>= 60 mL/min * Urine protein must be screened by urine analysis within 28 days prior to registration; patient must not have greater than +1 proteinuria on two consecutive dipsticks taken no less than 7 days apart; however, if the first urinalysis shows no protein, then a repeat urinalysis is not required * Patient must have an electrocardiogram (ECG) performed within 42 days prior to registration; patient must not have mean corrected QT (QTc) \> 500 msec (with Bazett's correction) in screening electrocardiogram, or other significant ECG abnormality, New York Heart Association (NYHA) classification III or IV; patient must not require concurrent use of drugs or biologics with proarrhythmic potential * Patient must not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine) * Patient must not have had clinically significant hemoptysis, defined as greater than 1 tablespoon of bright red blood, within one year prior to registration; although hemoptysis has not been associated with cediranib, it may be a class effect for anti-angiogenic agents and therefore a risk factor for this experimental agent * Patient must be able to swallow oral medications * Patients must not have known human immunodeficiency virus (HIV) infection * Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * Patient must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy or any other type of therapy for treatment of cancer while on this protocol treatment * No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose of Cediranib in Combination With Cisplatin and Pemetrexed (Phase I) | Weekly during first cycle (1cycle = 21 days). Then will be reported every cycle while patient is on treatment. | MTD was determined by testing dose-de-escalation to 20mg PO daily on dose de-escalation cohort 1 to 2 with 3 to 6 patients each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. Toxicities will be graded according to the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events. Dose-limiting toxicities (DLT) apply only during Cycle 1 and must be drug-related (i.e. possibly, probably or definitely related to one of the 3 study drugs). The following events occurring in the first cycle of treatment are considered dose limiting. 1. Febrile neutropenia 2. Grade 4 neutrophil count decrease for more than 7 days' duration 3. Grade 4 platelet count decrease 4. Grade 3 or 4 non-hematologic toxicity (excluding alopecia) |
| Progression-free Survival (Phase II) | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever came first, assessed up to 5 years.Disease assessment will be repeated every 6 weeks until disease progression. | From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesions, or the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate by RECIST1.1 (Phase II) | Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years. Best response is documented for as long as the patient remains on protocol treatment. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline. |
| Disease Control Rate by RECIST 1.1 (Phase II) | Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control rate is documented for as long as the patient remains on protocol treatment. | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA): Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA All target measurable lesions must be assessed using the same techniques as baseline. |
| Response Rate by Modified RECIST (Phase II) | Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Best response is documented for as long as the patient remains on protocol treatment. | Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline. |
| Disease Control Rate by Modified RECIST (Phase II) | Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control is documented for as long as the patient remains on protocol treatment. | Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA), does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA. All target measurable lesions must be assessed using the same techniques as baseline. |
| (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Toxicity assessment is repeated every 3 weeks while patient is on treatment. | Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Toxicity assessment is repeated weekly during first cycle (1cycle = 21 days), then every cycle while patient is on treatment. | Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
| Overall Survival (Phase II) | From date of registration to death.Disease assessment will be repeated every 6 weeks until disease progression. After progression, follow up will occur every 6 months for the first two years and then at the end of the third year after registration. | From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAnne S Tsao
SWOG Cancer Research Network
Participant flow
Recruitment details
117 participants were enrolled, only 112 participants were included in the analysis: 5 patients were either not eligible or not analyzable. Thus these 5 patients were excluded from any analysis.
Participants by arm
| Arm | Count |
|---|---|
| Phase I All Participants All participants from Phase I | 20 |
| Phase II Cisplatin-pemetrexed Cediranib 20mg Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and cediranib maleate PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cediranib maleate alone PO QD in the absence of disease progression or unacceptable toxicity.
Cediranib Maleate: Given orally
Cisplatin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pemetrexed Disodium: Given IV | 45 |
| Phase II Cisplatin-pemetrexed Placebo Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 2 hours on day 1 and placebo PO QD on days 1-21. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive placebo alone PO QD in the absence of disease progression or unacceptable toxicity.
Placebo: Given orally
Cisplatin: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pemetrexed Disodium: Given IV | 47 |
| Total | 112 |
Baseline characteristics
| Characteristic | Total | Phase II Cisplatin-pemetrexed Placebo | Phase II Cisplatin-pemetrexed Cediranib 20mg | Phase I All Participants |
|---|---|---|---|---|
| Age, Continuous | 69.8 years | 71.8 years | 71.3 years | 64.4 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 104 Participants | 44 Participants | 41 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Histology Biphasic or sarcomatoid | 25 Participants | 12 Participants | 11 Participants | 2 Participants |
| Histology Epitheliod or mesothelioma, NOS | 87 Participants | 35 Participants | 34 Participants | 18 Participants |
| Measurable Disease per Modified RECIST for Pleural Tumors Measurable | 85 Participants | 30 Participants | 36 Participants | 19 Participants |
| Measurable Disease per Modified RECIST for Pleural Tumors Non-measurable | 27 Participants | 17 Participants | 9 Participants | 1 Participants |
| Measurable Disease per RECIST 1.1 Measurable | 92 Participants | 40 Participants | 35 Participants | 17 Participants |
| Measurable Disease per RECIST 1.1 Non-measurable | 20 Participants | 7 Participants | 10 Participants | 3 Participants |
| Prior history of definitive surgery No | 91 Participants | 41 Participants | 33 Participants | 17 Participants |
| Prior history of definitive surgery Yes | 21 Participants | 6 Participants | 12 Participants | 3 Participants |
| Prior history of radiation No | 90 Participants | 38 Participants | 37 Participants | 15 Participants |
| Prior history of radiation Yes | 22 Participants | 9 Participants | 8 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 100 Participants | 42 Participants | 43 Participants | 15 Participants |
| Sex: Female, Male Female | 19 Participants | 7 Participants | 7 Participants | 5 Participants |
| Sex: Female, Male Male | 93 Participants | 40 Participants | 38 Participants | 15 Participants |
| Zubrod Performance Status 0-1 | 105 Participants | 44 Participants | 42 Participants | 19 Participants |
| Zubrod Performance Status 2 | 7 Participants | 3 Participants | 3 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 7 | 9 / 13 | 39 / 45 | 41 / 47 |
| other Total, other adverse events | 7 / 7 | 13 / 13 | 42 / 44 | 43 / 46 |
| serious Total, serious adverse events | 4 / 7 | 6 / 13 | 32 / 44 | 25 / 46 |
Outcome results
Primary
Maximum Tolerated Dose of Cediranib in Combination With Cisplatin and Pemetrexed (Phase I)
MTD was determined by testing dose-de-escalation to 20mg PO daily on dose de-escalation cohort 1 to 2 with 3 to 6 patients each. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in \> 33% of participants. Toxicities will be graded according to the CTEP Active Version of the NCI Common Terminology Criteria for Adverse Events. Dose-limiting toxicities (DLT) apply only during Cycle 1 and must be drug-related (i.e. possibly, probably or definitely related to one of the 3 study drugs). The following events occurring in the first cycle of treatment are considered dose limiting. 1. Febrile neutropenia 2. Grade 4 neutrophil count decrease for more than 7 days' duration 3. Grade 4 platelet count decrease 4. Grade 3 or 4 non-hematologic toxicity (excluding alopecia)
Time frame: Weekly during first cycle (1cycle = 21 days). Then will be reported every cycle while patient is on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase I Participants | Maximum Tolerated Dose of Cediranib in Combination With Cisplatin and Pemetrexed (Phase I) | 20 mg |
Primary
Progression-free Survival (Phase II)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesions, or the appearance of new lesions.
Time frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever came first, assessed up to 5 years.Disease assessment will be repeated every 6 weeks until disease progression.
Population: Only eligible and analyzable patients were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Phase I Participants | Progression-free Survival (Phase II) | 7.2 month |
| Phase II Cisplatin-pemetrexed Placebo | Progression-free Survival (Phase II) | 5.6 month |
p-value: 0.0680% CI: [0.54, 0.95]Log Rank
Secondary
Disease Control Rate by Modified RECIST (Phase II)
Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA), does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA. All target measurable lesions must be assessed using the same techniques as baseline.
Time frame: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control is documented for as long as the patient remains on protocol treatment.
Population: Eligible patients with baseline measurable disease per modified RECIST were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase I Participants | Disease Control Rate by Modified RECIST (Phase II) | 75 percentage of analyzed participants |
| Phase II Cisplatin-pemetrexed Placebo | Disease Control Rate by Modified RECIST (Phase II) | 83 percentage of analyzed participants |
p-value: 0.1995% CI: [0.18, 1.94]Chi-squared
Secondary
Disease Control Rate by RECIST 1.1 (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (STA): Does not qualify for CR, PR, Progression or Symptomatic Deterioration. Disease Control Rate (DCR) = CR + PR + STA All target measurable lesions must be assessed using the same techniques as baseline.
Time frame: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Disease control rate is documented for as long as the patient remains on protocol treatment.
Population: Eligible patients with baseline eligible disease per RECIST 1.1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase I Participants | Disease Control Rate by RECIST 1.1 (Phase II) | 74 percentage of analyzed participants |
| Phase II Cisplatin-pemetrexed Placebo | Disease Control Rate by RECIST 1.1 (Phase II) | 80 percentage of analyzed participants |
p-value: 0.0995% CI: [0.14, 1.49]Chi-squared
Secondary
Overall Survival (Phase II)
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time frame: From date of registration to death.Disease assessment will be repeated every 6 weeks until disease progression. After progression, follow up will occur every 6 months for the first two years and then at the end of the third year after registration.
Population: Only eligible and analyzable patients are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| All Phase I Participants | Overall Survival (Phase II) | 10 month |
| Phase II Cisplatin-pemetrexed Placebo | Overall Survival (Phase II) | 8.5 month |
p-value: 0.2880% CI: [0.65, 1.17]Log Rank
Secondary
(Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Toxicity assessment is repeated every 3 weeks while patient is on treatment.
Population: Patients who received at least one dose of protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypocalcemia | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Delirium | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 4 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 5 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 3 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute coronary syndrome | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Epistaxis | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Intracranial hemorrhage | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duodenal hemorrhage | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 4 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 6 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 6 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Non-cardiac chest pain | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions-Other | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 4 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 7 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal and urinary disorders - Other, specify | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest wall pain | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Glucose intolerance | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Seizure | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus bradycardia | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hearing impaired | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 3 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial flutter | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 2 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 4 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 3 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 0 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound dehiscence | 1 Participants |
| All Phase I Participants | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 9 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Wound dehiscence | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Delirium | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Acute coronary syndrome | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 7 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anorexia | 4 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial fibrillation | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Chest wall pain | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Creatinine increased | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Death NOS | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Duodenal hemorrhage | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Epistaxis | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fall | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 5 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | General disorders and admin site conditions-Other | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Generalized muscle weakness | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Glucose intolerance | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Headache | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hearing impaired | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyperglycemia | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypocalcemia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypotension | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypoxia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Intracranial hemorrhage | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lung infection | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 5 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 8 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Non-cardiac chest pain | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Rash maculo-papular | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Renal and urinary disorders - Other, specify | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Respiratory failure | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Seizure | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Sinus bradycardia | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Supraventricular tachycardia | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Syncope | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Thromboembolic event | 3 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Urinary tract infection | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 4 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase II) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Atrial flutter | 1 Participants |
Secondary
(Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Toxicity assessment is repeated weekly during first cycle (1cycle = 21 days), then every cycle while patient is on treatment.
Population: Patients who received at least one dose of protocol treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 2 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 1 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Irregular menstruation | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 2 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 1 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 1 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 0 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 1 Participants |
| All Phase I Participants | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Palmar-plantar erythrodysesthesia syndrome | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Irregular menstruation | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Weight loss | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hyponatremia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Lymphocyte count decreased | 0 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Abdominal pain | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Peripheral sensory neuropathy | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Anemia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Mucositis oral | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Constipation | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Vomiting | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dehydration | 3 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Fatigue | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Diarrhea | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nausea | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Dyspnea | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Platelet count decreased | 3 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Gastrointestinal disorders - Other, specify | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Nervous system disorders - Other, specify | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Heart failure | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | White blood cell decreased | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypertension | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Neutrophil count decreased | 2 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypokalemia | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Pulmonary hypertension | 1 Participants |
| Phase II Cisplatin-pemetrexed Placebo | (Phase I) Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Hypomagnesemia | 0 Participants |
Secondary
Response Rate by Modified RECIST (Phase II)
Per modified RECIST for Pleural Tumors. In addition to RECIST1.1, for modified RECIST, measurements based on the sum of 6 CT cuts in the pleural perpendicular to the chest wall are applied to standard RECIST criterial (sum of 6 = one univariate diameter). Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline.
Time frame: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years.Best response is documented for as long as the patient remains on protocol treatment.
Population: Eligible patients with baseline measurable disease per modified RECIST were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase I Participants | Response Rate by Modified RECIST (Phase II) | 50 percentage of analyzed participants |
| Phase II Cisplatin-pemetrexed Placebo | Response Rate by Modified RECIST (Phase II) | 20 percentage of analyzed participants |
p-value: 0.00695% CI: [1.4, 13.3]Chi-squared
Secondary
Response Rate by RECIST1.1 (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. All target measurable lesions must be assessed using the same techniques as baseline.
Time frame: Disease assessment will be repeated every 6 weeks until disease progression, up to 3 years. Best response is documented for as long as the patient remains on protocol treatment.
Population: Only eligible patients with baseline measurable disease per RECIST 1.1 were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Phase I Participants | Response Rate by RECIST1.1 (Phase II) | 26 percentage of analyzed participants |
| Phase II Cisplatin-pemetrexed Placebo | Response Rate by RECIST1.1 (Phase II) | 15 percentage of analyzed participants |
p-value: 0.1595% CI: [0.59, 5.83]Chi-squared