Combination Of Lapatinib With Carboplatin, Paclitaxel, and With or Without Trastuzumab In Metastatic Breast Cancer.
- Conditions
- Neoplasms, Breast
- Interventions
- Registration Number
- NCT00367471
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
The purpose of this study is to determine the optimally-tolerated regimens (OTR) for lapatinib in combination with paclitaxel, carboplatin with and without trastuzumab in patients with metastatic breast cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group B paclitaxel Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin. Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks. Group A lapatinib Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks. Group A trastuzumab Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks. Group A carboplatin Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks. Group A paclitaxel Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes. Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion. Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15). Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks. Group B lapatinib Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin. Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks. Group B carboplatin Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28). Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin. Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks.
- Primary Outcome Measures
Name Time Method Adverse events and safety evaluations 28 days * The OTR for Treatment Group A (lapatinib, paclitaxel, carboplatin, and trastuzumab) will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle.
* The OTR for Treatment Group B (lapatinib, paclitaxel, carboplatin) will be defined as the maximum dose level at which no more than one subject out of six experiences a DLT after completing one treatment cycle.
* Adverse events and changes from baseline in laboratory values, Multiple-gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.
- Secondary Outcome Measures
Name Time Method Tumor response by RECIST version 1.0 From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months Tumor response is assessed using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. RECIST has 4 response categories:
* Complete Response (CR) = disappearance of all target and non-target lesions.
* Partial Response (PR) = at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of diameters.
* Progressive Disease (PD) = At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
* Stable Disease (SD) = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
A CR or PR should be confirmed within 4 weeks.Duration of Response (DOR) From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months Duration of Response is defined as the time from the first documented evidence of CR or PR until the first documented sign of PD or death due to breast cancer.
Progression-free survival (PFS) From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months Progression-free survival is defined as the time from first dose until the first documented sign of disease progression or death due to any cause. For subjects who do not progress or die, but who permanently discontinue Lapatinib treatment, progression-free survival will be censored at the time of last radiological scan preceding the initiation of alternative anti-cancer therapy. For subjects who do not progress or die and who complete the study, progression-free survival will be censored at the time of last radiological scan preceding the date of the study conclusion.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸Greensboro, North Carolina, United States