A Study of First Line Treatment With Avastin (Bevacizumab) in Combination With Carboplatin and Weekly Paclitaxel in Patients With Ovarian Cancer

Study Overview
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Brief Summary
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This single arm study evaluated the efficacy and safety of first-line chemotherapy with carboplatin and dose-dense weekly paclitaxel plus bevacizumab (Avastin) in participants with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Participants received 6-8 3-week cycles of treatment with bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m^2 iv on days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve (AUC) of 6 on day 1 of each cycle. Following combination chemotherapy, bevacizumab could be continued to be given as a monotherapy.

Official Title
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A Single-arm Phase II Clinical Study Investigating the Addition of Bevacizumab to Carboplatin and Weekly Paclitaxel as First-line Treatment in Patients With Epithelial Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Female patients, ≥ 18 years of age. Epithelial ovarian, fallopian tube, or primary peritoneal cancer. Initial surgery, but no chemotherapy or radiotherapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Exclusion Criteria Non-epithelial tumors. Ovarian tumors with low malignant potential. Previous systemic anti-cancer therapy for ovarian cancer. History or evidence of synchronous primary endometrial cancer. Current or recent daily treatment with aspirin (> 325mg/day) or with full dose anticoagulant or thrombolytic agents for therapeutic purposes.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab + paclitaxel + carboplatin<br>Participants received 6-8 (at the investigator's discretion) 3-week cycles of bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m^2 iv on Days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). Following the combination treatments, participants received up to 17 3-week cycles of bevacizumab 7.5 mg/g iv alone. | Drug: Bevacizumab<br>* Bevacizumab was supplied as a sterile solution for infusion.<br>* Other names: Avastin;Drug: Paclitaxel<br>* Paclitaxel was supplied locally in commercial batches.<br>* Other names: Taxol;Drug: Carboplatin<br>* Carboplatin was supplied locally in commercial batches.<br>* Other names: Paraplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first. | Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Objective Response | An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level. | Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month) | 
| Duration of Response | Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level. | Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month) | 
| Overall Survival at 1 Year and 2 Years | Reported are the percentage of participants that were alive at 1 year and 2 years after enrolling in the study. | Baseline to Year 2 | 
| Biological Progression-free Interval | Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for patients with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment and initial normalisation of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per patient on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment which never normalised). | Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month) |