Clinical Trial: Gemcitabine Hydrochloride With or Without Pazopanib Hydrochloride in Treating Patients With Refractory Soft Tissue Sarcoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized, Double-Blind Phase II, Study of Gemcitabine Alone or in Combination With Pazopanib for Refractory Soft Tissue Sarcoma

Brief Summary: This randomized phase II trial studies how well gemcitabine hydrochloride works with or without pazopanib hydrochloride in treating patients with refractory soft tissue sarcoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride, 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 some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether gemcitabine hydrochloride is more effective with or without pazopanib hydrochloride in treating patients with soft tissue sarcoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To investigate whether treatment with gemcitabine (gemcitabine hydrochloride) plus pazopanib (pazopanib hydrochloride) improves the median progression-free survival of patients with metastatic soft tissue sarcoma when compared to gemcitabine plus placebo.

SECONDARY OBJECTIVES:

I. To assess response rate in this population to gemcitabine plus pazopanib compared to gemcitabine plus placebo.

II. To assess overall survival in this population to gemcitabine plus pazopanib compared to gemcitabine plus placebo.

III. To investigate differences in treatment response in different histologic subgroups (liposarcoma vs. all other eligible soft tissue sarcoma subtypes).

IV. To evaluate the safety and tolerability of the combination of gemcitabine plus pazopanib.

V. To assess the progression-free survival and response rate in patients treated with single agent pazopanib following administration of gemcitabine in the cross-over portion of this study.

VI. To collect specimens for an exploratory analysis of potential biomarkers that predict response in patients receiving combination therapy with gemcitabine plus pazopanib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8 and pazopanib hydrochloride orally (PO) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Sponsor: OHSU Knight Cancer Institute

Current Primary Outcome: Progression-free survival (PFS) [ Time Frame: Calculated as the time from randomization to the first documented progression or death whichever occurs first, or until time of last contact if no progression or death occurred, assessed up to 3 years ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Best overall response rate [ Time Frame: Best response recorded from the start of treatment until disease progression/recurrence assessed up to 3 years ]
  Estimated odds ratio of treatment response will be reported with 95% confidence interval for the two histologic sarcoma subgroups (liposarcoma vs. all other eligible soft tissue sarcoma subtypes). Exact one-sided CMH test will be used to determine whether the response rates differ for the subgroups in general.
• Incidence of adverse events and serious adverse events, defined using the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0. [ Time Frame: Up to 3 years ]
  Toxicities will be descriptively tabulated. Frequency and severity of adverse events will be tabulated for each treatment arm based on the actual treatment the patient receives. Toxicity and adverse events will be summarized according to each major organ group and grade outline in the CTCAE v4.0 criteria.
• Overall survival [ Time Frame: From randomization to death due to any cause, or until last patient contact if the patient did not die, assessed up to 3 years ]
  Two treatment arms will be compared using a one-sided log-rank test stratified by sarcoma subtype and study site. Kaplan-Meier estimates and the survival curves for each treatment arm will be presented with the estimated hazard ratios and their associated confidence interval.
• PFS (for a sub-group of patients treated with single-agent pazopanib hydrochloride following administration of gemcitabine hydrochloride in the cross-over portion of this study) [ Time Frame: Calculated as the time from receiving open-labeled pazopanib hydrochloride to the next documented progression or death whichever occurs first, assessed up to 3 years ]
  Statistical analysis is exploratory—Kaplan-Meier estimate and the survival curve will be presented with the estimated hazard ratio and its associated 95% confidence interval.
• Response rate [ Time Frame: Assessed up to 3 years ]
  Categorized into complete response, partial response, progressive disease, and stable disease following RECIST version 1.1. Estimated odds ratio of treatment response will be reported with 95% confidence interval for the two histologic sarcoma subgroups (liposarcoma vs. all other eligible soft tissue sarcoma subtypes). Exact one-sided Cochran-Mantel-Haenszel (CMH) test will be used to determine whether the response rates differ for the subgroups in general.

Original Secondary Outcome:

• PFS (for a sub-group of patients treated with single-agent pazopanib hydrochloride following administration of gemcitabine hydrochloride in the cross-over portion of this study) [ Time Frame: Calculated as the time from receiving open-labeled pazopanib hydrochloride to the next documented progression or death whichever occurs first, assessed up to 3 years ]
• Response rate (RR) [ Time Frame: Assessed up to 3 years ]
• Best overall response rate (ORR) [ Time Frame: Assessed up to 3 years ]
• Overall survival (OS) [ Time Frame: From randomization to death due to any cause, or until last patient contact if the patient did not die, assessed up to 3 years ]
• Adverse events and serious adverse events, defined using the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0. [ Time Frame: The duration of the study, up to 3 years ]

Dates:
Date Received: February 6, 2012
Date Started: March 2012
Date Completion: March 2018
Last Updated: May 1, 2017
Last Verified: May 2017