- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00887822
A Study of Bevacizumab (Avastin) Versus Placebo in Combination With Capecitabine (Xeloda) and Cisplatin as First-Line Therapy for Advanced Gastric Cancer (AVATAR)
January 10, 2017 updated by: Hoffmann-La Roche
A Double-Blind, Randomized, Multicenter, Phase III Study of Bevacizumab in Combination With Capecitabine and Cisplatin Versus Placebo in Combination With Capecitabine and Cisplatin, as First-Line Therapy in Patients With Advanced Gastric Cancer.
This 2 arm study will compare the efficacy and safety of bevacizumab in combination with capecitabine and cisplatin versus placebo in combination with capecitabine and cisplatin in participants who have not received prior chemotherapy for advanced or metastatic gastric cancer.
Participants will be randomized to one of two treatment groups Bevacizumab + Capecitabine/Cisplatin (experimental arm) or Placebo + Capecitabine/Cisplatin (control arm).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
202
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Beijing, China, 100021
-
Beijing, China, 100142
-
Beijing, China, 100071
-
Beijing, China, 100853
-
ChongQing, China, 400042
-
Guangzhou, China, 510060
-
Hangzhou, China, 310016
-
Nanjing, China
-
Nanjing, China, 210036
-
Shanghai, China, 200032
-
Shanghai, China, 200080
-
Shantou, China, 515041
-
Shenyang, China, 110001
-
Wuhan, China, 430030
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction with inoperable, locally advanced or metastatic disease, not amenable to curative therapy
- Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
- Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
Exclusion Criteria:
- Previous chemotherapy for locally advanced or metastatic gastric cancer
- Previous platinum or anti-angiogenic therapy
- Radiotherapy within 28 days of randomization
- Evidence of Central Nervous System (CNS) metastasis at baseline
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Bevacizumab, Capecitabine and Cisplatin
Participants will receive bevacizumab 7.5 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 of every 3-week cycle in combination with capecitabine 1000 milligrams per square meter (mg/m^2) orally twice daily (total daily dose 2000 mg/m^2) on Days 1-14 of every 3-week cycle and cisplatin 80 mg/m^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles; until disease progression or unmanageable toxicity.
|
7.5 mg/kg IV infusion on Day 1 of every 3-week cycle
Other Names:
1000 mg/m^2 orally twice daily on Days 1-14 of every 3-week cycle
Other Names:
80 mg/m^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles
|
Placebo Comparator: Placebo, Capecitabine and Cisplatin
Participants will receive placebo matched to bevacizumab on Day 1 of every 3-week cycle in combination with capecitabine 1000 mg/m^2 orally twice daily (total daily dose 2000 mg/m^2) on Days 1-14 of every 3-week cycle and cisplatin 80 mg/m^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles; until disease progression or unmanageable toxicity.
|
1000 mg/m^2 orally twice daily on Days 1-14 of every 3-week cycle
Other Names:
80 mg/m^2 IV infusion on Day 1 of every 3-week cycle for a maximum of 6 cycles
Placebo matched to bevacizumab on Day 1 of every 3-week cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Event (Death)
Time Frame: From randomization until death (up to 34 months)
|
Percentage of participants who died due to any cause was reported.
As planned, ad hoc analysis was done for overall survival up to clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months).
Overall survival was defined as the time between randomization and the date of death due to any cause.
|
From randomization until death (up to 34 months)
|
Overall Survival
Time Frame: From randomization until death (up to 34 months)
|
Overall survival was defined as the time between randomization and the date of death due to any cause.
Overall survival was estimated using Kaplan Meier method.
Reported data included censored observations.
Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive.
As planned, ad hoc analysis was done for overall survival up to clinical clinical cut-off date of 12 January 2012 (34 months), subsequent to the protocol-defined clinical cut-off date of 13 May 2011 (26 months).
|
From randomization until death (up to 34 months)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Progression-Free Survival (PFS) Events (Disease Progression/Death)
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Progression of disease was defined as at least 20 percent (%) increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 millimeters (mm), progression of existing non-target lesions, or presence of new lesions.
PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to Response Evaluation Criteria In Solid Tumors (RECIST).
|
From randomization until disease progression or death (up to 26 months)
|
Progression-Free Survival (PFS)
Time Frame: From randomization until disease progression or death (up to 26 months)
|
PFS was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first, according to RECIST.
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
PFS was estimated using Kaplan Meier method.
Reported data included censored observations.
Participants who had neither progressed nor died at the time of study completion or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease.
Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
|
From randomization until disease progression or death (up to 26 months)
|
Percentage of Participants With PFS Events (Disease Progression/Death) During First-line Therapy
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
PFS during first-line therapy was defined as the time between randomization and the date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last confirmed intake of any study medication and before the start of non-study antineoplastic treatment, according to RECIST.
|
From randomization until disease progression or death (up to 26 months)
|
PFS During First-line Therapy
Time Frame: From randomization until disease progression or death (up to 26 months)
|
PFS during first-line therapy was defined as time between randomization and date of first documented disease progression or death, whichever occurred first and only if it occurred no later than 28 days after last intake of any study medication and only if it occurred before start of non-study antineoplastic treatment, according to RECIST.
Progression of disease was defined as at least 20% increase in sum of longest diameters of target lesions compared to smallest sum of longest diameters on-study & absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
PFS was estimated using Kaplan Meier method.
Reported data included censored observations.
Participants who neither progressed nor died in this interval, or who were lost to follow-up were censored at date of last tumor assessment/last follow-up within this time window.
Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
|
From randomization until disease progression or death (up to 26 months)
|
Percentage of Participants With Disease Progression
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
|
From randomization until disease progression or death (up to 26 months)
|
Time to Progression
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Time to progression was defined as the time between randomization and the first occurrence of disease progression.
Progression of disease was defined as at least 20% increase in the sum of longest diameters of target lesions compared to the smallest sum of longest diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
Time to progression was estimated using Kaplan Meier method.
Reported data included censored observations.
Participants who had not progressed at the time of study completion (including participants who had died before disease progression) or who were lost to follow-up were censored at the date of the last tumor assessment or last follow-up for progression of disease.
Participants for whom no post-baseline tumor assessments were available were censored at day of randomization.
|
From randomization until disease progression or death (up to 26 months)
|
Percentage of Participants With Best Overall Response as Assessed by RECIST During First-Line Therapy
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Best overall response during first-line therapy was defined as the occurrence of either a confirmed complete (CR) or a partial response (PR), as assessed by the RECIST criteria.
CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers.
Pathological lymph nodes must have short axis measures less than (<) 10 mm.
PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters.
|
From randomization until disease progression or death (up to 26 months)
|
Duration of Response During First-Line Therapy
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Duration of response during first-line therapy was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first) during first-line therapy.
CR: disappearance of all target and non-TLs and normalization of tumor markers.
Pathological lymph nodes must have short axis measures <10 mm.
PR: at least a 30 % decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of longest diameters.
Duration of response was estimated using Kaplan Meier method.
Reported data included censored observations.
Participants who did not progress or die after they had had a confirmed response were censored at the date of their last tumor measurement or last follow-up for progression of disease during first line therapy.
|
From randomization until disease progression or death (up to 26 months)
|
Percentage of Participants With Disease Control During First-Line Therapy
Time Frame: From randomization until disease progression or death (up to 26 months)
|
Disease control was defined as stable disease(SD) for 6 weeks or longer, CR plus PR as assessed by RECIST criteria for participants with measurable disease.CR:disappearance of all TLs & normalization of tumor markers.
Pathological lymph nodes must have short axis measures<10 mm.
PR:at least 30% decrease in sum of measures(longest diameter for tumor lesions and short axis measure for nodes)of TLs, taking as reference baseline sum of longest diameters.SD:neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression taking as reference smallest sum of longest diameters on study.
For participants without measurable disease, clinical benefit rate was defined as no clinical disease progression for >/=6 weeks.
Disease progression was defined as at least 20% increase in sum of diameters of TLs compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.
|
From randomization until disease progression or death (up to 26 months)
|
Change From Cycle 1 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 36 (QLQ-C30) Scale Over Time
Time Frame: From Cycle 1 until disease progression (up to 26 months)
|
EORTC QLQ-C30 included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, and financial difficulties).
Most questions used a 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used a 7-point scale (1 'Very Poor' to 7 'Excellent').
Scores were averaged and transformed to 0-100 scale; a higher score for Global Qol/functional scales=better level of QoL/functioning, or a higher score for symptom scale=greater degree of symptoms.
|
From Cycle 1 until disease progression (up to 26 months)
|
Change From Cycle 1 in EORTC QLQ-STO22 Scale Over Time
Time Frame: From Cycle 1 until disease progression (up to 26 months)
|
The EORTC QLQ-STO22 is a gastric cancer quality of life questionnaire.
There are 22 questions which comprise 5 scales (dysphagia, pain, reflux symptom, dietary restrictions, and anxiety) and 4 single items (dry mouth, hair loss, taste, body image).
Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer).
A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100; higher score=better level of functioning or greater degree of symptoms.
|
From Cycle 1 until disease progression (up to 26 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2009
Primary Completion (Actual)
May 1, 2011
Study Completion (Actual)
August 1, 2014
Study Registration Dates
First Submitted
April 22, 2009
First Submitted That Met QC Criteria
April 23, 2009
First Posted (Estimate)
April 24, 2009
Study Record Updates
Last Update Posted (Actual)
March 1, 2017
Last Update Submitted That Met QC Criteria
January 10, 2017
Last Verified
January 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Stomach Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Cisplatin
- Capecitabine
- Bevacizumab
Other Study ID Numbers
- ML22367
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Gastric Cancer
-
City of Hope Medical CenterRecruitingGastric Cancer | Gastric Adenocarcinoma | Gastric Cancer Stage IV | Gastric Neoplasm | Gastric Cancer Metastatic to Lung | Gastric Cancer Stage | Gastric Cancer Metastatic to Liver | Gastric Cancer Stage III | Gastric Cancer Stage II | Gastric Lesion | Gastric Cancer in Situ | Gastric Cancer Stage IIIB | Gastric... and other conditionsUnited States, Japan
-
City of Hope Medical CenterNational Cancer Institute (NCI)Active, not recruitingGastric Adenocarcinoma | Clinical Stage III Gastric Cancer AJCC v8 | Clinical Stage 0 Gastric Cancer AJCC v8 | Clinical Stage I Gastric Cancer AJCC v8 | Clinical Stage II Gastric Cancer AJCC v8 | Clinical Stage IIA Gastric Cancer AJCC v8 | Clinical Stage IIB Gastric Cancer AJCC v8 | Pathologic Stage... and other conditionsUnited States
-
City of Hope Medical CenterActive, not recruitingAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Diffuse Adenocarcinoma of the Stomach | Intestinal Adenocarcinoma of the Stomach | Mixed Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric Cancer and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingGastric Adenocarcinoma | Clinical Stage III Gastric Cancer AJCC v8 | Clinical Stage I Gastric Cancer AJCC v8 | Clinical Stage IIA Gastric Cancer AJCC v8 | Clinical Stage IVA Gastric Cancer AJCC v8 | Pathologic Stage IB Gastric Cancer AJCC v8 | Pathologic Stage II Gastric Cancer AJCC v8 | Pathologic... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedGastric Adenocarcinoma | Stage IV Gastric Cancer | Stage II Gastric Cancer | Stage III Gastric CancerUnited States
-
Mayo ClinicNational Cancer Institute (NCI)CompletedGastroesophageal Junction Adenocarcinoma | Gastric Cardia Adenocarcinoma | Stage IB Gastric Cancer AJCC v7 | Stage II Gastric Cancer AJCC v7 | Stage IIA Gastric Cancer AJCC v7 | Stage IIB Gastric Cancer AJCC v7 | Stage IIIA Gastric Cancer AJCC v7 | Stage IIIB Gastric Cancer AJCC v7United States
-
National Cancer Institute (NCI)CompletedAdenocarcinoma of the Gastroesophageal Junction | Stage IV Gastric Cancer | Recurrent Gastric Cancer | Adenocarcinoma of the Stomach | Stage IIIA Gastric Cancer | Stage IIIB Gastric Cancer | Stage IIIC Gastric CancerUnited States
-
National Cancer Institute (NCI)CompletedGastric Cancer | Gastric NeoplasmsUnited States
-
AIO-Studien-gGmbHBristol-Myers SquibbCompletedGastric Cancer | Esophageal Cancer | Adenocarcinoma Gastric | Metastatic Gastric Cancer | GastroEsophageal Cancer | HER2 Positive Gastric CancerGermany
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI)RecruitingGastric Adenocarcinoma | Epstein-Barr Virus Positive | Mismatch Repair Protein Deficiency | Stage IB Gastric Cancer AJCC v7 | Stage II Gastric Cancer AJCC v7 | Stage IIA Gastric Cancer AJCC v7 | Stage IIB Gastric Cancer AJCC v7 | Stage III Gastric Cancer AJCC v7 | Stage IIIA Gastric Cancer AJCC v7 | Stage... and other conditionsUnited States
Clinical Trials on Bevacizumab
-
National Cancer Institute (NCI)Active, not recruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Serous Cystadenocarcinoma | Endometrial Clear Cell Adenocarcinoma | Endometrial Serous Adenocarcinoma | Recurrent... and other conditionsUnited States
-
National Cancer Institute (NCI)NRG OncologyCompletedGlioblastoma | Gliosarcoma | Recurrent Glioblastoma | Oligodendroglioma | Giant Cell Glioblastoma | Recurrent Brain NeoplasmUnited States, Canada
-
M.D. Anderson Cancer CenterRecruitingStage IB Hepatocellular Carcinoma AJCC v8 | Stage II Hepatocellular Carcinoma AJCC v8 | Resectable Hepatocellular Carcinoma | Stage I Hepatocellular Carcinoma AJCC v8 | Stage IA Hepatocellular Carcinoma AJCC v8United States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)RecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Fallopian Tube Clear Cell Adenocarcinoma | Fallopian Tube Endometrioid Adenocarcinoma | Fallopian Tube Serous Adenocarcinoma and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingOvarian Endometrioid Adenocarcinoma | Primary Peritoneal High Grade Serous Adenocarcinoma | Fallopian Tube Endometrioid Adenocarcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Ovarian High Grade Serous Adenocarcinoma | Platinum-Resistant... and other conditionsUnited States, Canada
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingMalignant Solid Neoplasm | Ovarian Endometrioid Adenocarcinoma | Ovarian Undifferentiated Carcinoma | Cervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Malignant Peritoneal Neoplasm | Endometrial Clear Cell Adenocarcinoma | Endometrial Endometrioid Adenocarcinoma | Endometrial Mixed Cell... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedCervical Adenocarcinoma | Cervical Adenosquamous Carcinoma | Cervical Squamous Cell Carcinoma, Not Otherwise Specified | Stage IVA Cervical Cancer AJCC v6 and v7 | Recurrent Cervical Carcinoma | Stage IV Cervical Cancer AJCC v6 and v7 | Stage IVB Cervical Cancer AJCC v6 and v7United States
-
Northwestern UniversityNational Cancer Institute (NCI); Ipsen BiopharmaceuticalsCompletedRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Platinum-Resistant Fallopian Tube Carcinoma | Platinum-Resistant Primary Peritoneal Carcinoma | Platinum-Resistant Ovarian Carcinoma | Refractory Ovarian Carcinoma | Refractory Fallopian Tube... and other conditionsUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); Merck Sharp & Dohme LLC; Celldex TherapeuticsRecruitingRecurrent Fallopian Tube Carcinoma | Recurrent Ovarian Carcinoma | Recurrent Primary Peritoneal Carcinoma | Recurrent Endometrial Serous Adenocarcinoma | Ovarian Clear Cell Adenocarcinoma | Recurrent Platinum-Resistant Ovarian Carcinoma | Platinum-Sensitive Ovarian Carcinoma | Recurrent Fallopian... and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingStage IV Cutaneous Melanoma AJCC v6 and v7 | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable MelanomaUnited States