Neoplasms, Breast
Conditions
Keywords
breast cancer
Brief summary
This Study was designed to determine how effective and safe a new investigational drug, lapatinib, is in combination with paclitaxel in treating patients with newly diagnosed inflammatory breast cancer. Tumor tissue collected pre-treatment, following 14 days of treatment and at the time of surgical resection will be examined for pathologic response and biologic activity by IHC (immunohistochemistry) within the tumor. Treatment will consist of 14 days of lapatinib monotherapy followed by 12 weeks of combination therapy with lapatinib and paclitaxel. Blood samples for hematology and chemistry panels, MUGA/ECHO exams and physical exams will be performed throughout the study to monitor safety.
Interventions
DRUGLapatinib
Daily-monotherapy \[1500 milligrams (mg)\] for 14 days, then daily combination therapy (with weekly paclitaxel) for 12 weeks
DRUGPaclitaxel
Weekly (80mg/m\^2) combination therapy (with daily Lapatinib) for 12 weeks
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Tumor accessible for multiple biopsies * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Adequate bone marrow * Renal and hepatic function * LVEF (left ventricular ejection fraction) greater than 0% based on ECHO (echocardiogram) or MUGA (multigated acquisition).
Exclusion criteria
* Females who are pregnant or nursing. * Any unstable, pre-existing major medical condition. * Received an investigational drug within the past 4 weeks. * Had major surgery in the past 2 weeks. * Currently receiving amiodarone or has received amiodarone in the past 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with pathologic complete response rate (pCR) | Week 12 | pCR was defined as the percentage of participants who achieved an assessment of complete response (CR) following pathologic review of resected tissue. CR was the disappearance of all target lesions. Participants in each cohort with unknown or missing response (i.e., those that did not undergo surgery) were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population response was considered to be of special interest. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with objective response rate (ORR) at the end of study (Response evaluation criteria in solid tumor [RECIST]) | Week 14 | ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or partial response (PR) at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using RECIST criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be of special interest. |
| Percentage of participants with ORR at the end of study (Clinically Evaluable Skin Disease Criteria) | Week 14 | ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using Clinically Evaluable Skin Disease Criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, HER2+ population was considered to be of special interest. |
| Percentage of participants with ORR at the end of study ('Best' of RECIST and Clinically Evaluable Skin Disease Criteria) | Week 14 | ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. The best response of the participant was defined by the 'Best' combined response (RECIST and Clinically Evaluable Skin Disease Criteria) provided there is no evidence of disease progression. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be special interest. |
| Percentage of participants with investigator-Assessed Best Response at the end of monotherapy phase (Day 14) (Clinically Evaluable Skin Disease Criteria) | Day 14 | ORR at the end of the monotherapy phase was defined as the percentage of participants within each cohort who had a confirmed CR or PR at the end of lapatinib monotherapy (Day 14) divided by the total number of participants enrolled in each cohort. CR was the disappearance of all target lesions. PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter. Each participant's response was based on the investigator assessment of best response using clinically evaluable skin disease criteria. Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population was considered to be special interest. |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Up to Week 14, surgical resection and post treatment | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect, resulted in deterioration in left ventricular cardiac function and caused Grade 3 or 4 interstitial pneumonitis. |
| Number of participants with shift from Baseline in hematological toxicity grade | Day 14 and up to Week 23, surg resection and post treatment | Hematology was summarized for hemoglobin (Hb), platelets, white blood cell count (WBC), neutrophils (Neu), lymphocytes by scheduled assessment and also according to the maximum common terminology criteria (CTC) toxicity grade. Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib. Change from Baseline was calculated as the value at each visit minus Baseline value. |
| Percentage of participants with pCR that underwent surgical resection | Week 12 | pCR for participants that underwent surgical (surg) resection was defined as the percentage of participants within each cohort who achieved an assessment of CR following pathologic review of resected tissue. CR was the disappearance of all target lesions. Participants in each cohort that did not undergo surgical resection were excluded from the denominator when calculating the percentage. From an efficacy standpoint, the HER2+ population response was considered to be of special interest. |
| Change from Baseline in vital signs- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) | Day 14, Week 1 and up to Week 24, surg resection and post treatment | Vitals signs (SBP and DBP) were assessed from screening until the post treatment phase. Baseline was the most recent blood pressure (BP) mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline. |
| Change from Baseline in vital signs- Heart Rate (HR) | Day 14, Week 1 and up to Week 24, surg resection and post treatment | Vitals signs (HR) were assessed from screening until the post treatment phase. Baseline was the most recent BP mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline. |
| Change from Baseline in vital signs- Body temperature | Day 14, Week 1 and up to Week 24, surg resection and post treatment | Vitals signs (body temperature) were assessed from screening until the post treatment phase. Baseline was the most recent BP mean prior to the first dose of lapatinib. Change from Baseline was calculated as the mean at each visit minus the mean at Baseline. |
| Number of participants with abnormal electrocardiogram (ECG) findings | Screening and unscheduled | ECG was performed at screening and at unscheduled visits. Participants with abnormal clinically significant and abnormal not clinically significant ECG findings was reported. |
| Number of participants with change from Baseline in echocardiogram (ECHO) or Multi-gated angiogram (MUGA) results at any post Baseline visit | Screening, Week 8, 16, 24, post treatment | For ECHO and MUGA scans, the left ventricular ejection fraction (percent) was summarized for each scheduled assessment. Absolute change from Baseline was summarized according to the following categories: any increase, 0 to less than 20 percent decrease, \>=20 percent decrease or \>=20 percent decrease and below the lower limit of normal (LLN). Baseline was the most recent ECOG evaluation prior to the first dose of lapatinib. Change from Baseline was calculated as the value at the post treatment minus Baseline value. |
| Number of participants with shift from Baseline in clinical chemistry toxicity grade | Day 14, Week 4, 8, 12, 16, 20, Surg resection and post treatment | Clinical chemistry was summarized for sodium, potassium (K), bicarbonate (bicarb), albumin (alb), calcium, gamma glutamyl transferase (GGT), creatinine (creat), total bilirubin (TB), alkaline phosphatase (ALP), aspartate amino transferase (AST) and alanine amino transferase (ALT) by scheduled assessment and also according to the maximum CTC toxicity grade. Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib. Change from Baseline was calculated as the value at each visit minus Baseline value. |
Countries
Australia, Canada, France, Israel, New Zealand, Spain, Tunisia, United Kingdom, United States
Outcome results
None listed