Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Persistent or Recurrent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer
This randomized phase II trial is studying how well giving paclitaxel with or without pazopanib hydrochloride works in treating patients with persistent or recurrent ovarian epithelial, fallopian tube, or peritoneal cavity cancer. Drugs used in chemotherapy, such as paclitaxel work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking blood flow to the tumor or by blocking some of the enzymes needed for cell growth. It is not yet known whether paclitaxel is more effective when given with or without pazopanib hydrochloride in treating ovarian epithelial, fallopian tube, and peritoneal cavity cancer
Recurrent Fallopian Tube Cancer
Recurrent Ovarian Epithelial Cancer
Recurrent Primary Peritoneal Cavity Cancer
Drug: pazopanib hydrochloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||A Randomized Phase IIB Evaluation of Weekly Paclitaxel (NSC #673089) Plus Pazopanib (NSC #737754) (IND #75648) Versus Weekly Paclitaxel Plus Placebo in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma|
- Efficacy of each treatment regimen [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Evaluated using the Cox proportional hazards and stratified by platinum-free interval, measurable disease status, and prior use of bevacizumab. Maximum likelihood estimate of the logarithm of the hazard ratio of Arm 2 to Arm 1 for disease progression or death (PFS endpoint) will be calculated.
- Adverse events as assessed by CTCAE [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Toxicities will be characterized by their frequency and severity. Differences in the level of toxicities by treatment regimen will be assessed by classifying them as severe or not severe and examining the relative proportion of severe toxicities.
- Frequency and duration of tumor response by RECIST, including CA-125 status [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The effects of treatment on the proportion responding by RECIST and possibly by CA125 will be examined. An examination of response by CA125 (stratified by treatment) will also be conducted in those patients who have measurable disease to assess the level of agreement between the two methods of evaluation. The impact of additional, various prognostic factors or biological markers will be examined with exploratory analyses including log-rank tests with characterization with hazard ratio estimates.
- Overall survival (OS) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Differences between measurable versus non-measurable disease status on OS will be examined with plots of survival curves, estimates of quartiles and hazard ratios.
|Study Start Date:||December 2011|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Placebo Comparator: Arm I (paclitaxel and placebo)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Other Name: PLCBDrug: paclitaxel
Experimental: Arm II (paclitaxel and pazopanib hydrochloride)
Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Other Names:Drug: paclitaxel
I. To estimate the progression-free survival hazard ratio of the combination of weekly paclitaxel and pazopanib (pazopanib hydrochloride) compared to weekly paclitaxel and placebo in patients with persistent or recurrent ovarian, fallopian tube, or primary peritoneal cancer.
I. To determine the frequency and severity of adverse events as assessed by CTCAE.
II. To estimate and compare the proportion of patients responding to therapy by RECIST, CA125 response, the overall survival (OS), and the duration of response in each arm.
I. To explore the association between plasma cytokines and angiogenic markers and progression-free and overall survival.
II. To explore the association between single-nucleotide polymorphisms (SNPs) and progression-free and overall survival.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo orally (PO) daily on days 1-28.
ARM II: Patients receive paclitaxel as in arm I and pazopanib hydrochloride PO daily on days 1-28.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.