Ph II Study of Wkly Topotecan + Bevacizumab in Plat. Resistant/Recurrent Gyn Cancers

Phase 2

Completed

Brief Summary: The purpose of this study is to evaluate the clinical safety and toxicity of intravenous bevacizumab (Days 1 and 15 of a 28 day cycle) in combination with weekly topotecan (Days 1, 8, 15 of a 28 day cycle) in patients with platinum resistant recurrent ovarian, fallopian tube and primary peritoneal cancer.

Detailed Description: This study is designed as a Phase 2 study. There are no published data on the toxicity of the combination of bevacizumab and topotecan therapy. Based on data combining bevacizumab with other chemotherapy agents in non-gynecologic solid tumors, it is not likely that the toxicity of the combination of the two drugs will be greater than the individual toxicities of each drug. The toxicities of each of these agents is quite different. Specifically the toxicity of this combination will be studied using the dose of bevacizumab used in previous phase II studies of ovarian cancer, e.g. an equivalent of 5 mg/kg weekly with treatments given at least every 3 weeks. In our study, since topotecan will be given weeks 1,2 and 3 of an every 4 week cycle, it is convenient to give bevacizumab 10 mg/kg IV every other week.

Recruitment & Eligibility

Inclusion Criteria

must have received primary taxane and platinum-based chemotherapy and no more than 1 other chemotherapy regimen
must have platinum resistant disease(defined as recurrence within 6 months of receiving platinum based chemotherapy, first or second line)
must have measurable disease (greater than 20mm by conventional techniques or 10mm by spiral CT) OR elevated CA-125 (> 100 on two occasions at least one week apart
performance status greater than or equal to 70%

Exclusion Criteria

prior treatment with anti-angiogenesis agent
treatment with > 2 cytotoxic regimens (including primary platinum and taxane chemotherapy)
evidence of other malignancy within 3 years of study enrollment
history of abdominal fistula, grade 4 bowel obstruction or gastrointestinal perforation
history of intra-abdominal abscess with 6 months prior to day 0
pregnant or lactating patients

Arm && Interventions

Group	Intervention	Description
Treatment	Topotecan	Subjects received standard topotecan with the addition of bevacizumab. Cycles were 28 days and continued until toxicity, progression or subject wish to discontinue treatment. Topotecan administered 4 mg/m2 IV on days 1, 8 and 15 and bevacizumab IV 10 mg/kg, days 1 and 15 of each cycle.
Treatment	Bevacizumab	Subjects received standard topotecan with the addition of bevacizumab. Cycles were 28 days and continued until toxicity, progression or subject wish to discontinue treatment. Topotecan administered 4 mg/m2 IV on days 1, 8 and 15 and bevacizumab IV 10 mg/kg, days 1 and 15 of each cycle.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival	PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.	Progression free survival(PFS)was measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with measurable disease. For patients with nonmeasurable disease, cancer antigen (CA-125) levels were used to determine response according to Rustin criteria. Progression-free survival was defined as number of months after beginning study treatment until progressive disease or death, respectively.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	Response	RECIST criteria
Number or Participants With Toxicity	measured at each treatment cycle
Evaluation of Overall Survival	PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.	Overall survival was defined as the number of months after commencing study treatment to death.

Locations (2): Puget Sound Oncology Consortium (PSOC)
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Seattle, Washington, United States
Virginia Mason Medical Center
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Seattle, Washington, United States