Pazopanib Hydrochloride, Paclitaxel, and Carboplatin in Treating Patients With Refractory or Resistant Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer
RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
PURPOSE: This randomized phase I/II trial is studying the side effects and best dose of pazopanib hydrochloride when given together with paclitaxel and carboplatin in treating patients with refractory or resistant ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer.
|Fallopian Tube Cancer Ovarian Cancer Primary Peritoneal Cavity Cancer||Drug: carboplatin Drug: paclitaxel Drug: pazopanib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study||Phase 1 Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase IB-II, Open Label, Multicenter Feasibility Study of Pazopanib in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory/Resistant Ovarian, Fallopian Tube or Peritoneal Carcinoma|
- Maximum-tolerated dose of pazopanib hydrochloride, carboplatin, and paclitaxel (phase I)
- Progression-free survival according to RECIST 1.1 at 1 year (phase II)
- Pharmacokinetics of pazopanib, carboplatin, and paclitaxel (phase I)
- Safety and tolerability according to CTCAE 4.0 (phase I and phase II)
- Response rate (phase I and phase II)
- Predictive biomarkers (phase I and phase II)
- Overall survival (phase II)
- Age-related subanalysis for toxicity and efficacy (cut-off 65 years old) (phase II)
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||May 2019 (Final data collection date for primary outcome measure)|
Experimental: pazopanib in combination with paclitaxel and carboplatin
Phase I: Dose-escalation study of pazopanib in combination with paclitaxel and carboplatin given weekly in a group of patients with platinum-refractory or -resistant ovarian, fallopian tube or peritoneal carcinoma Phase II: Paclitaxel 30 mg/m² and Carboplatin 2.0 AUC weekly for 18 courses PLUS Pazopanib 400 mg daily
|Drug: carboplatin Drug: paclitaxel Drug: pazopanib hydrochloride Other: laboratory biomarker analysis Other: pharmacological study|
Active Comparator: Paclitaxel and carboplatin only
Carboplatin AUC 2.7 and paclitaxel 60mg/m² weekly for 18 courses.
|Drug: carboplatin Drug: paclitaxel Drug: pazopanib hydrochloride|
- To determine the maximum-tolerated dose of pazopanib hydrochloride in combination with paclitaxel and carboplatin in patients with platinum-refractory or -resistant ovarian epithelial, fallopian tube, or peritoneal carcinoma. (Phase I)
- To determine the progression-free survival (PFS) at 1 year according to the RECIST 1.1 in these patients. (Phase II)
- To determine the safety and adverse event profiles in these patients. (Phase I and phase II)
- To determine the pharmacokinetics (PK) of this regimen using intensive sampling. (Phase I)
- To determine if there is PK interaction (and if so, what kind of PK interaction) between carboplatin and paclitaxel as well as pazopanib hydrochloride. (Phase I)
- To determine the response rate (RR) in these patients. (Phase I)
- To determine and evaluate predictive biomarkers. (Phase I and phase II)
- To determine the RR, overall survival (OS), and PFS of these patients. (Phase II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of carboplatin, paclitaxel, and pazopanib hydrochloride followed by a phase II randomized study.
- Phase I: Patients receive paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes on day 1. Patients also receive oral pazopanib hydrochloride* once daily on days 2-7. Treatment repeats every week for up to 18 courses**. Patients then continue to receive oral pazopanib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
NOTE: *Pazopanib hydrochloride is started in course 2 in order to evaluate the pharmacokinetic of paclitaxel and carboplatin prior to pazopanib hydrochloride administration.
Phase II: Patients are stratified according to center, disease status (platinum-refractory vs -resistant) and number of prior lines of treatment (1 vs more than 1). Patients are randomized in a 2:1 ratio (arm II [experimental arm]: arm I [standard arm]) to 1 of 2 treatment arms.
- Arm I (standard arm): Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Treatment repeats every week for up to 18 courses.
- Arm II (experimental arm): Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Patients also receive oral pazopanib hydrochloride once daily on days 2-7. Treatment repeats every week for up to 18 courses**. Patients then continue to receive oral pazopanib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
NOTE: **After course 9, chemotherapy will be interrupted for 1 week.
Blood samples are collected from some patients periodically for pharmacokinetic and biomarker studies.
After completion of study treatment, patients are followed up at 3 weeks, every 3 months for 2 years, and then every 6 months for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01402271
|Contact: Ellen Peetersemail@example.com|
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|Principal Investigator: Joseph Kerger|
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|Principal Investigator: Frederic Kridelka|
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|Principal Investigator: Chantal Leroy|
|ZNA Jan Palfijn||Recruiting|
|Principal Investigator: Aldrik Nielander|
|Radboud University Medical Center Nijmegen||Recruiting|
|Principal Investigator: Nelleke Ottevanger|
|Contact: Ingrid Boere, MD,PhD|
|Principal Investigator: Ingrid Boere, MD, PhD|
|Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)||Recruiting|
|Principal Investigator: Margarita Romeo|
|Hospital Clínico Universitario San Carlos||Recruiting|
|Contact: Antonio Casado, MD, PhD|
|Principal Investigator: Antonio Casado, MD, PhD|
|Study Chair:||Ignace B. Vergote, MD, PhD||University Hospital, Gasthuisberg|
|Principal Investigator:||Ingrid Boere, MD, PhD||Erasmus MC|
|Principal Investigator:||Antonio Casado, MD, PhD||Hospital Clínico Universitario San Carlos|