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
OBJECTIVES:
Primary
- 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)
Secondary
- 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.
Interventional
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of pazopanib hydrochloride, carboplatin, and paclitaxel (phase I)
Yes
Ignace B. Vergote, MD, PhD
Study Chair
U.Z. Gasthuisberg
Belgium: Federal Agency for Medicinal Products and Health Products
EORTC-55092
NCT01402271
July 2012
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