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

• Progression-free survival.
• The difference in incidences of NCI CTCAE Grade 1 unexplainable gastrointestinal perforation or Grade 2 and higher gastrointestinal perforation

• Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: From randomization through September 17, 2010 ] [ Designated as safety issue: No ]
  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.
• Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: From randomization through September 17, 2010 ] [ Designated as safety issue: No ]
  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.
• Overall Survival [ Time Frame: From randomization through September 17, 2010 ] [ Designated as safety issue: No ]
  Overall survival was defined as the time from randomization to death from any cause.
• Percentage of Patients Who Had a Gastrointestinal Perforation (GIP) [ Time Frame: From first treatment through September 17, 2010 ] [ Designated as safety issue: Yes ]
  A gastrointestinal perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder.
• Percentage of Patients Who Had at Least 1 Adverse Event [ Time Frame: From first treatment through September 17, 2010 ] [ Designated as safety issue: Yes ]

• Objective response
• Overall survival
• Duration of objective response.

This is a placebo-controlled, randomized, multicenter Phase III study evaluating 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.

• Drug: Carboplatin
  Carboplatin was provided as commercially available drug.
• Drug: Gemcitabine
  Gemcitabine was provided as commercially available drug.
• Drug: Bevacizumab
  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.
  Other Name: Avastin
• Drug: Placebo
  Placebo consisted of the vehicle for bevacizumab without the antibody and contained sodium phosphate, trehalose, polysorbate 20, and Sterile Water for Injection, USP.

• Experimental: Carboplatin and gemcitabine + bevacizumab
  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.
  Interventions:

  • Drug: Carboplatin
  • Drug: Gemcitabine
  • Drug: Bevacizumab
• Active Comparator: Carboplatin and gemcitabine + placebo
  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.
  Interventions:

  • Drug: Carboplatin
  • Drug: Gemcitabine
  • Drug: Placebo

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)