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

Sponsor:	Genentech
Information provided by (Responsible Party):	Genentech
ClinicalTrials.gov Identifier:	NCT00434642

Purpose

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.

Condition	Intervention	Phase
Ovarian Cancer	Drug: Carboplatin Drug: Gemcitabine Drug: Bevacizumab Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Carboplatin Gemcitabine Gemcitabine hydrochloride Bevacizumab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

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 ]

Enrollment:	484
Study Start Date:	April 2007
Estimated Study Completion Date:	October 2013
Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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
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.	Drug: Carboplatin Carboplatin was provided as commercially available drug. Drug: Gemcitabine Gemcitabine was provided as commercially available drug. 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.

Arms

Assigned Interventions

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.

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

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.

Drug: Carboplatin

Carboplatin was provided as commercially available drug.

Drug: Gemcitabine

Gemcitabine was provided as commercially available drug.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434642

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Amreen Husain, MD

Genentech

More Information

No publications provided by Genentech

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00434642 History of Changes
Other Study ID Numbers:	AVF4095g
Study First Received:	February 9, 2007
Results First Received:	September 26, 2011
Last Updated:	September 26, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

Avastin
Ovarian carcinoma
Peritoneal carcinoma
Peritoneal cancer

Fallopian tube cancer
Fallopian tube carcinoma
OCEANS

Additional relevant MeSH terms:

Carcinoma
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

Fallopian Tube Diseases
Gemcitabine
Bevacizumab
Carboplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 13, 2012