A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-line Therapy in Patients With Advanced Gastric Cancer

NCT00548548 | Completed Phase 3 Results

• 2 other identifiers: AVF4200gBO20904
• Study Type: interventional
• Target: 774
• Locations: 1 country
• Sites: 13

Brief Summary

This study will compare treatment with bevacizumab in combination with capecitabine and cisplatin versus placebo in combination with capecitabine and cisplatin, as first-line therapy in patients with locally advanced or metastatic gastric cancer who had not received prior chemotherapy for advanced or metastatic disease.

Conditions

Adenocarcinoma

Keywords

Avastin; Metastatic Adenocarcinoma; AVAGAST

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The primary efficacy endpoint for this study was overall survival (time to death), defined as the time between randomization and the date of death irrespective of the cause of death. Patients for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Median survival was estimated by the Kaplan-Meier method.

  From randomization until death, up to 26 months

Secondary Outcomes (7)

• Progression-free Survival

  From randomization until disease progression or death, up to 26 months.

• Progression-free Survival During First-line Therapy

  From randomization until 28-days after the last study treatment was administered, up to 26 months.

• Time to Disease Progression

  From randomization until disease progression; assessed every 6 weeks for the first year and every 12 weeks thereafter, up to 26 months.

• Participants With a Best Overall Response of Complete or Partial Response

  From randomization until the end of study, up to 26 months.

• Duration of Response

  From randomization to the end of study, up to 26 months

Study Arms (2)

Bevacizumab

EXPERIMENTAL

Participants received intravenous (IV) bevacizumab 7.5 mg/kg every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. Bevacizumab and capecitabine/5-FU were administered until disease progression or unacceptable toxicity.

Drug: Bevacizumab; Drug: Capecitabine; Drug: Cisplatin; Drug: 5-fluorouracil

Placebo

PLACEBO COMPARATOR

Participants received intravenous (IV) placebo infusion every 3 weeks, oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, or 5-fluorouracil (5-FU) at a dose of 800 mg/m˄2/day as a continuous IV infusion over the first 5 days of every 3 week cycle, and cisplatin 80 mg/m˄2 as an IV infusion every 3 weeks for a maximum of 6 cycles. The placebo and capecitabine/5-FU were administered until disease progression or unacceptable toxicity.

Drug: Capecitabine; Drug: Cisplatin; Drug: Placebo; Drug: 5-fluorouracil

Interventions

Bevacizumab DRUG

Intravenous bevacizumab 7.5 mg/kg once every 3 weeks, given until disease progression or unmanageable toxicity.

Bevacizumab

Capecitabine DRUG

Oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, given until disease progression or unmanageable toxicity.

Bevacizumab; Placebo

Cisplatin DRUG

Cisplatin 80 mg/m˄2 as a 2 hr intravenous infusion with hyper-hydration and pre-medication (steroids and anti-emetics), given every 3 weeks for a maximum of 6 cycles or until disease progression or unmanageable toxicity.

Bevacizumab; Placebo

Placebo DRUG

Intravenous placebo every 3 weeks, given until disease progression or unmanageable toxicity.

Placebo

5-fluorouracil DRUG

For participants with difficulty swallowing, malabsorption, or other conditions that could affect intake of oral capecitabine medication, 5-fluorouracil was administered instead, at a dose of 800 mg/m˄2/day as a continuous intravenous infusion over 5 days (days 1 to 5 of each cycle), every 3 weeks.

Bevacizumab; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained prior to any study specific procedures.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Life expectancy of at least 3 months.
• Able to comply with the protocol.
• Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable, locally advanced, or metastatic disease, not amenable to curative therapy.
• Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST).
• Patient not receiving anticoagulant medication must have an International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x Upper Limit of Normal (ULN) within 7 days prior to randomisation.

You may not qualify if:

• Previous chemotherapy for locally advanced or metastatic gastric cancer. Patients may have received prior neoadjuvant or adjuvant chemotherapy as long as it was completed at least 6 months prior to randomisation.
• Previous platinum or anti-angiogenic therapy (ie, anti-vascular endothelial growth factor \[VEGF\] or VEGF receptor tyrosine kinase inhibitor, etc.).
• Patients with locally advanced disease who are candidates for curative therapy (including operation and/or chemotherapy and/or radiotherapy).
• Radiotherapy within 28 days of randomisation.
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomisation, or anticipation of the need for major surgery during the course of the study treatment (planned elective surgery).
• Minor surgical procedures within 2 days prior to randomisation.
• Evidence of central nervous system (CNS) metastasis at baseline.
• History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately treated with standard medical therapy, eg, uncontrolled seizures.
• History of another malignancy which could affect compliance with the protocol or interpretation of results.
• Inadequate bone marrow function.
• Inadequate liver function.
• Inadequate renal function.
• Uncontrolled hypertension or clinically significant (ie, active) cardiovascular disease.
• Active infection requiring intravenous antibiotics at randomisation.
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.

Sponsors & Collaborators

• Genentech, Inc.: lead
• Hoffmann-La Roche: collaborator
• Chugai Pharmaceutical: collaborator

Study Sites (13)

Tower Cancer Research Fnd

Beverly Hills, California, 90211-1850, United States

Location

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

Kenmar Research Institute LLC

Los Angeles, California, 90057, United States

Location

USC/Norris Cancer Center

Los Angeles, California, 90089, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

H. Lee Moffitt Cancer

Tampa, Florida, 33612, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214-3728, United States

Location

Methodist Cancer Center Onc

Omaha, Nebraska, 68114, United States

Location

Memorial Sloan Kettering

New York, New York, 10021, United States

Location

Duke Univ Medical Center

Durham, North Carolina, 27710, United States

Location

South Carolina Oncology Assoc

Columbia, South Carolina, 10595, United States

Location

The Sarah Cannon Research Inst

Nashville, Tennessee, 37203, United States

Location

Related Publications (2)

• Han K, Jin J, Maia M, Lowe J, Sersch MA, Allison DE. Lower exposure and faster clearance of bevacizumab in gastric cancer and the impact of patient variables: analysis of individual data from AVAGAST phase III trial. AAPS J. 2014 Sep;16(5):1056-63. doi: 10.1208/s12248-014-9631-6. Epub 2014 Jun 19.

  PMID: 24942210 DERIVED

• Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. doi: 10.1200/JCO.2011.36.2236. Epub 2011 Aug 15.

  PMID: 21844504 DERIVED

MeSH Terms

Conditions

Adenocarcinoma

Interventions

Bevacizumab; Capecitabine; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• Eric Hedrick, MD

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2007
• First Posted: October 24, 2007
• Study Start: September 1, 2007
• Primary Completion: November 1, 2009
• Study Completion: November 1, 2013
• Last Updated: June 14, 2017
• Results First Posted: January 19, 2012

Record last verified: 2017-05

Locations

US (13)