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

• ClinicalTrials.gov Identifier: NCT00434642
• Recruitment Status: Completed
• First Posted: February 13, 2007
• Results First Posted: November 3, 2011
• Last Update Posted: August 9, 2017
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: February 9, 2007
• First Posted Date: February 13, 2007
• Results First Submitted Date: September 26, 2011
• Results First Posted Date: November 3, 2011
• Last Update Posted Date: August 9, 2017
• Study Start Date: April 2007
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2014)

Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: From randomization through September 17, 2010 (up to 3 years, 5 months) ]

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.

Original Primary Outcome Measures (submitted: February 9, 2007)

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

Current Secondary Outcome Measures (submitted: September 26, 2014)

• 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 (up to 3 years, 5 months) ]
  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 (up to 3 years, 5 months) ]
  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 July 19, 2013 (up to 6 years, 3 months) ]
  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 randomization through September 17, 2010 (up to 3 years, 5 months) ]
  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 randomization through July 19, 2013 (up to 6 years, 3 months) ]

Original Secondary Outcome Measures (submitted: February 9, 2007)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Ovary, Peritoneal, or Fallopian Tube Carcinoma
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• 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.

Study Arms

• 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

Publications *

• Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015 Oct;139(1):10-6. doi: 10.1016/j.ygyno.2015.08.004. Epub 2015 Aug 10.
• Vaughan S, Coward JI, Bast RC Jr, Berchuck A, Berek JS, Brenton JD, Coukos G, Crum CC, Drapkin R, Etemadmoghadam D, Friedlander M, Gabra H, Kaye SB, Lord CJ, Lengyel E, Levine DA, McNeish IA, Menon U, Mills GB, Nephew KP, Oza AM, Sood AK, Stronach EA, Walczak H, Bowtell DD, Balkwill FR. Rethinking ovarian cancer: recommendations for improving outcomes. Nat Rev Cancer. 2011 Sep 23;11(10):719-25. doi: 10.1038/nrc3144.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2011): 484
• Original Enrollment (submitted: February 9, 2007): 200
• Actual Study Completion Date: July 2013
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT00434642
• Other Study ID Numbers: AVF4095g
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Not Provided
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Amreen Husain, MD; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: July 2017