A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma

Study Overview
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Brief Summary
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This is a placebo-controlled, randomized, multicenter Phase III study that will evaluate the safety and efficacy of bevacizumab, administered in combination with carboplatin with gemcitabine, in women with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinoma.

Official Title
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A Phase III, Multicenter, Randomized, Blinded, Placebo-controlled Trial of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Platinum-sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Drug: Gemcitabine
* Drug: Bevacizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form Age ≥ 18 years Documented ovarian, primary peritoneal, or fallopian tube carcinoma that has recurred No prior chemotherapy in the recurrent setting Measurable disease Recovered from prior radiation therapy or surgery Exclusion Criteria: Prior chemotherapy treatment for recurrent ovarian, primary peritoneal, or fallopian tube carcinoma History of abdominal fistula, gastrointestinal perforation (GIP), or intra-abdominal abscess Patients with clinical symptoms or signs of gastrointestinal (GI) obstruction or who require parenteral hydration, parenteral nutrition, or tube feeding Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure Current, recent, or planned participation in an experimental drug study History of systemic bevacizumab (Avastin) or other vascular endothelial growth factor (VEGF) or VEGF receptor-targeted agent use Inadequately controlled hypertension Prior history of hypertensive crisis or hypertensive encephalopathy New York Heart Association Class II or greater congestive heart failure (CHF) History of myocardial infarction or unstable angina History of stroke or transient ischemic attack (TIA) Known central nervous system (CNS) disease except for treated brain metastasis Significant vascular disease or recent peripheral arterial thrombosis History of hemoptysis Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Carboplatin and gemcitabine + bevacizumab<br>Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Bevacizumab 15 mg/kg was administered IV on Day 1 of each of the six 21-day treatment cycles. The bevacizumab dose was based on the patient's weight at baseline and remained the same throughout the study. | Drug: Carboplatin<br>* Carboplatin was provided as commercially available drug.<br>Drug: Gemcitabine<br>* Gemcitabine was provided as commercially available drug.<br>Drug: Bevacizumab<br>* Bevacizumab was supplied as a clear to slightly opalescent, sterile liquid in glass vials (400 mg in 8 mL [25 mg/mL]) with a vehicle consisting of sodium phosphate, trehalose, polysorbate 20, and Sterile Water for Injection, USP.<br>* Other names: Avastin;|
| Active Comparator: Carboplatin and gemcitabine + placebo<br>Carboplatin (AUC 4 mg/mL/minute) was administered intravenously (IV) on Day 1 of each of six 21-day treatment cycles. The carboplatin dose was calculated to reach a target area under the curve (AUC) of concentration x time according to the Calvert formula. Gemcitabine 1000 mg/m^2 was administered IV on Days 1 and Day 8 of each of the six 21-day treatment cycles. Placebo was administered by IV on Day 1 of each of the six 21-day treatment cycles. | Drug: Carboplatin<br>* Carboplatin was provided as commercially available drug.<br>Drug: Gemcitabine<br>* Gemcitabine was provided as commercially available drug.<br>Drug: Placebo<br>* Placebo consisted of the vehicle for bevacizumab without the antibody and contained sodium phosphate, trehalose, polysorbate 20, and Sterile Water for Injection, USP.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) | PFS was defined as the time from randomization to disease progression (PD), as determined by the investigator, or death due to any cause. PD: 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; the appearance of 1 or more new lesions; and/or the unequivocal progression of existing non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. | From randomization through September 17, 2010 (up to 3 years, 5 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) | An objective response was the occurrence of either a partial response (PR) or complete response (CR). PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. CR: The disappearance of all target and non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. | From randomization through September 17, 2010 (up to 3 years, 5 months) | 
| Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) | Duration of OR was analyzed in the subset of patients who achieved an OR. The duration of OR was defined as the time from the initial CR or PR until documented PD or death. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. | From randomization through September 17, 2010 (up to 3 years, 5 months) | 
| Overall Survival | Overall survival was defined as the time from randomization to death from any cause. | From randomization through July 19, 2013 (up to 6 years, 3 months) | 
| Percentage of Patients Who Had a Gastrointestinal Perforation (GIP) | A gastrointestinal perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder. | From randomization through September 17, 2010 (up to 3 years, 5 months) | 
| Percentage of Patients Who Had at Least 1 Adverse Event |  | From randomization through July 19, 2013 (up to 6 years, 3 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avastin, Ovarian carcinoma, Peritoneal carcinoma, Peritoneal cancer, Fallopian tube cancer, Fallopian tube carcinoma, OCEANS