Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cancer
Conditions
Keywords
platinum resistant ovarian cancer, recurrent ovarian cancer, platinum resistant cancer
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.
Interventions
DRUGTopotecan
Topotecan administered days 1, 8, and 15 of each 28 day cycle. Dose was 4 mg/m2 administered IV.
DRUGBevacizumab
bevacizumab administered IV 10 mg/kg, days 1 and 15 of 28 day cycle.
Sponsors
GlaxoSmithKline
Genentech, Inc.
Benaroya Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Objective Response Rate | Response | RECIST criteria |
| Number or Participants With Toxicity | measured at each treatment cycle | — |
Countries
United States
Participant flow
Recruitment details
Subjects enrolled from August 2006 to November 2008, in the medical oncoogy practices at Virginia Mason Medical Center and the Puget Sound Oncology Consortium in Seattle, WA.
Pre-assignment details
Women had advanced or recurrent epithelial ovarian, peritoneal, or fallopian tube cancer. Enrollment was restricted to women who had received a maximum of two prior chemotherapy regimens, with at least one prior primary taxane and platinum-based therapy.
Participants by arm
| Arm | Count |
|---|---|
| Combined Weekly Topotecan and Biweekly Bevacizumab Treatment was administered in 28 day cycles, with IV bevacizumab 10 mg/kg given on days 1 and 15 and IV topotecan 4 mg/m2 given on days 1 and 8. Treatment was continued until progressive disease defined by RECIST, symptomatic deterioration related to clinical progression, excessive toxicity. Dose reductions of bevacizumab were not permitted. | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Combined Weekly Topotecan and Biweekly Bevacizumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age, Continuous | 58.6 years STANDARD_DEVIATION 11.31 |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 40 |
| serious Total, serious adverse events | 9 / 40 |
Outcome results
Primary
Progression Free Survival
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.
Time frame: PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.
Population: This was determined assuming a median progression free survival of 9 months and an analysis calculating the sample size at which the narrowing of its 95% confidence interval became greater than .20 for every 2 patients added. Progression free survival and overall survival were estimated by using the Kaplan Meier method.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined Weekly Topotecan and Biweekly Bevacizumab | Progression Free Survival | One prior regimen (n=21) | 2.8 months |
| Combined Weekly Topotecan and Biweekly Bevacizumab | Progression Free Survival | Two prior regimens (n=19) | 10.9 months |
| Combined Weekly Topotecan and Biweekly Bevacizumab | Progression Free Survival | All participants | 7.8 months |
Comparison: Planned enrollment of 40 patients was determined assuming a median progression free survival (PFS) of 9 months (based on a median PFS of 7.2 months for low-dose, metronomic cyclophosphamide plus bevacizumab in a phase 2 study) and an analysis calculating the sample size at which the narrowing of its 95% confidence interval (CI) became greater than .2 for every 2 patients added. Progression free survival was estimated using the Kaplan-Meier method.p-value: 0.08Log Rank
Secondary
Evaluation of Overall Survival
Overall survival was defined as the number of months after commencing study treatment to death.
Time frame: PFS and OS were defined as the number of months after commencing study treatment until progressive disease or death.
Population: The planned enrollment of 40 participants was determined using a median PFS of 9 months (based on a median PFS of 7.2 months in a previous trial).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Combined Weekly Topotecan and Biweekly Bevacizumab | Evaluation of Overall Survival | All Participants | 16.6 months |
| Combined Weekly Topotecan and Biweekly Bevacizumab | Evaluation of Overall Survival | One Prior Regimen (n=21) | 12.8 months |
| Combined Weekly Topotecan and Biweekly Bevacizumab | Evaluation of Overall Survival | Two Prior Regimens (n=19) | 22.9 months |
Comparison: Overall survival(OS)was estimated using the Kaplan-Meier method.p-value: 0.02Log Rank
Secondary
Number or Participants With Toxicity
Time frame: measured at each treatment cycle
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Weekly Topotecan and Biweekly Bevacizumab | Number or Participants With Toxicity | 40 participants |
Secondary
Objective Response Rate
RECIST criteria
Time frame: Response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combined Weekly Topotecan and Biweekly Bevacizumab | Objective Response Rate | 10 participants |