Breast Cancer - Female, Unspecified Adult Solid Tumor - Protocol Specific
Conditions
Brief summary
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.
Detailed description
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).
Interventions
DRUGPazopanib
Starting dose is 400 given on Days 2-5, 9-12, and 16-26 of each 28 day cycle
DRUGPaclitaxel
Starting dose is 60 mg/m2 IV on days 1, 8, and 15 of each 28 day cycle
DRUGCarboplatin
Starting dose of carboplatin that corresponds to an AUC of 2, IV on days 1, 8, and 15 of each 28 day cycle
Sponsors
National Cancer Institute (NCI)
Rutgers Cancer Institute of New Jersey
GlaxoSmithKline
Rutgers, The State University of New Jersey
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of a solid malignancy with advanced disease that has relapsed, that is refractory to standard therapies, or for which there is not standard therapy, or for which the patient opts not to receive standard therapy. * At the recommended phase II dose level, triple-negative breast cancer defined as ER-negative, PR-negative, and HER2-negative, will be enrolled and another 10 patients with a solid malignancy who would benefit from a paclitaxel and carboplatin-based regimen, will also be enrolled. * Male or female ≥ 18 years of age * Able to swallow and retain oral medications
Exclusion criteria
* Major surgery within last 28 days or cytotoxic chemotherapy, biologic therapy, investigational agents, or radiotherapy within last 21 days. Patients who have completed therapy with mitomycin C or nitrosurea will have to wait 42 days. * More than 3 prior lines of cytotoxic chemotherapy for metastatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Establish the maximum tolerated dose (MTD) of pazopanib with weekly paclitaxel and carboplatin on a 28- day cycle | 4 years, 6 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the drug-drug interactions with paclitaxel, carboplatin, and pazopanib | 4 years, 3 months | 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 |
Countries
United States
Outcome results
None listed