This is an open label, dose escalation study to determine the safety and tolerability and maximum tolerated dose of pazopanib combined with weekly paclitaxel and carboplatin in patients with advanced solid tumors.
This is an open label, dose escalation study to determine the maximum tolerated dose (MTD) of pazopanib combined with weekly paclitaxel and carboplatin in patients with advanced solid tumors. There will be a dose expansion cohort of thirty patients to assess detailed pharmacokinetics and to assess any signal of activity in patients with solid tumors and in a portion who have breast cancer that is triple negative (ER-negative, PR-negative, and HER2-negative).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Starting dose is 400 given on Days 2-5, 9-12, and 16-26 of each 28 day cycle
Starting dose is 60 mg/m2 IV on days 1, 8, and 15 of each 28 day cycle
Starting dose of carboplatin that corresponds to an AUC of 2, IV on days 1, 8, and 15 of each 28 day cycle
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Establish the maximum tolerated dose (MTD) of pazopanib with weekly paclitaxel and carboplatin on a 28- day cycle
Toxicity will be assessed every 28 days up to 30 days after the last dose of treatment. Dose limiting toxicity is defined as 1. Non-hematological toxicity ≥ grade 3 (excluding alopecia, nausea, vomiting, or diarrhea for which adequate supportive therapy has not been instituted). 2. Hematologic toxicity: * Grade 4 neutropenia lasting ≥ 7 days * Grade 4 neutropenia and fever of ≥ 38.5°C * ≥ Grade 3 neutropenia with ≥ Grade 3 infection * Grade 4 thrombocytopenia * Inability to start next cycle of treatment by more than 4 weeks due to unresolved toxicity
Time frame: 4 years, 6 months
Determine the drug-drug interactions with paclitaxel, carboplatin, and pazopanib
The first 15 patients enrolled in the dose expansion cohort will undergo PK sampling as this is felt to be an adequate sample size. 4 blood samples (2 mL each) for the analysis of paclitaxel will be obtained in Cycle 1 Day 1 and Cycle 2 Day 1 2 blood samples (2 mL each) for the analysis of carboplatin will be obtained in Cycle 1 Day 1 and Cycle 2 Day 1 1 blood sample (2 mL) for the analysis of pazopanib will be collected in Cycle 2 Day 1
Time frame: 4 years, 3 months
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