Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00548548
Other study ID # AVF4200g
Secondary ID BO20904
Status Completed
Phase Phase 3
First received October 23, 2007
Last updated February 26, 2015
Start date September 2007
Est. completion date November 2013

Study information

Verified date February 2015
Source Genentech, Inc.
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


Description:

This is a 2 arm, randomized, double-blind, multicenter phase III study. Patients will be randomized (1:1) to capecitabine/cisplatin plus bevacizumab or capecitabine/cisplatin plus placebo. This is an event-driven trial with the primary analysis planned after approximately 517 deaths had been observed. After the primary analysis, the study will remain open and patients can continue with study treatment until progressive disease or earlier at the investigator's discretion. After discontinuation of the last patient, the study will end globally.


Recruitment information / eligibility

Status Completed
Enrollment 774
Est. completion date November 2013
Est. primary completion date November 2009
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- Serious or non-healing wound, peptic ulcer, or (incompletely healed) bone fracture.

- Active gastrointestinal bleeding.

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomisation.

- Neuropathy (eg, impairment of hearing and balance) = grade II according to Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

- Chronic daily treatment with aspirin or clopidogrel.

- Chronic daily treatment with oral corticosteroids; inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed.

- Known hypersensitivity to any of the study drugs or excipients or to Chinese hamster ovary cell products or to other recombinant human or humanised antibodies.

- Known dihydropyrimidine dehydrogenase (DPD) deficiency.

- Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that may affect patient compliance with the study, or place the patient at high risk from treatment complications.

- Known acute or chronic-active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).

- Pregnant or lactating females.

- Women of childbearing potential not using effective nonhormonal (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) means of contraception.

- Sexually active men unwilling to practice contraception during the study.

- Current or recent (within the 28 days prior to randomisation) treatment with another investigational drug or participation in another investigational study.

Study Design

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


Related Conditions & MeSH terms


Intervention

Drug:
Bevacizumab
Intravenous bevacizumab 7.5 mg/kg once every 3 weeks, given until disease progression or unmanageable toxicity.
Capecitabine
Oral capecitabine 1,000 mg/m^2 twice daily for 14 days every 3 weeks, given until disease progression or unmanageable toxicity.
Cisplatin
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.
Placebo
Intravenous placebo every 3 weeks, given until disease progression or unmanageable toxicity.
5-fluorouracil
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.

Locations

Country Name City State
United States Tower Cancer Research Fnd Beverly Hills California
United States South Carolina Oncology Assoc Columbia South Carolina
United States Duke Univ Medical Center Durham North Carolina
United States Florida Cancer Specialists Fort Myers Florida
United States Moores UCSD Cancer Center La Jolla California
United States Kenmar Research Institute LLC Los Angeles California
United States USC/Norris Cancer Center Los Angeles California
United States The Sarah Cannon Research Inst Nashville Tennessee
United States Memorial Sloan Kettering New York New York
United States Methodist Cancer Center Onc Omaha Nebraska
United States H. Lee Moffitt Cancer Tampa Florida
United States Georgetown University Washington District of Columbia
United States Cancer Center of Kansas Wichita Kansas

Sponsors (3)

Lead Sponsor Collaborator
Genentech, Inc. Chugai Pharmaceutical, Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Secondary Progression-free Survival Progression-free survival (PFS) is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first. Patients who 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. Median PFS was estimated using the Kaplan-Meier method. From randomization until disease progression or death, up to 26 months. No
Secondary Progression-free Survival During First-line Therapy Progression-free survival (PFS) during first-line therapy is defined as the time between randomization and the date of first documented disease progression or death, whichever occurs first and only if it occurs no later than 28 days after last confirmed intake of any study medication and only if it occurs before the start of non-study antineoplastic treatment. Participants who did not progress or die in this interval or were lost to follow-up were censored at the date of the last tumor assessment within this time window. Median PFS was estimated using the Kaplan-Meier method. From randomization until 28-days after the last study treatment was administered, up to 26 months. No
Secondary Time to Disease Progression Time to progression is defined as the time from randomization to the first occurrence of progressive disease (PD). PD was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria and defined as at least a 20% increase in the sum of the longest diameter of target lesions, or appearance of =1 new lesions and/or unequivocal progression of existing non-target lesions. Patients with no PD at study completion (including those who died before PD) were censored at the date of the last tumor assessment. Median time to PD was estimated using the Kaplan-Meier method. From randomization until disease progression; assessed every 6 weeks for the first year and every 12 weeks thereafter, up to 26 months. No
Secondary Participants With a Best Overall Response of Complete or Partial Response Best overall response during first-line therapy is defined as the occurrence of either a confirmed complete (CR) or a partial (PR) best overall response, as determined by the RECIST criteria. CR is defined as the disappearance of all target and non-target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions and no new or progression of non-target lesions, or the disappearance of all target lesions and persistence of one or more non-target lesion(s). From randomization until the end of study, up to 26 months. No
Secondary Duration of Response Duration of response during first line therapy is 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. This was only be calculated for participants who achieved a best overall response of CR or PR. Participants who did not progress or die after they 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. Median duration of response was estimated using the Kaplan-Meier method. From randomization to the end of study, up to 26 months No
Secondary Participants With Disease Control Disease control for participants with measurable disease was defined as a complete response (CR), partial response (PR) or stable disease (SD) for 6 weeks or longer, as determined by the RECIST criteria. For participants without measurable disease, disease control was defined as no disease progression for = 6 weeks. From randomization until the end of study, up to 26 months. No
Secondary Participants With Adverse Events The intensity of Adverse Events (AEs) was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0 on a five-point scale from Grade 1 (Mild) to Grade 5 (Death). A serious AE (SAE) was defined as any event that is fatal, life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. From randomization until 3 months after last dose (up to 26 months) No
See also
  Status Clinical Trial Phase
Recruiting NCT05678218 - Preoperative Evaluation of Lymph Nodes of Cholangiocarcinoma
Recruiting NCT05161572 - Perioperative Chemoimmunotherapy With/Without Preoperative Chemoradiation for Locally Advanced Gastric Cancer Phase 2
Recruiting NCT02292641 - Beyond TME Origins N/A
Withdrawn NCT05325164 - Methadone for 'Adenocarcinopathic' Pain Treatment Phase 3
Completed NCT02926768 - Phase I/II Study of CK-101 in NSCLC Patients and Other Advanced Solid Tumors Phase 1
Recruiting NCT02125240 - Icotinib Versus Placebo as Adjuvant Therapy in EGFR-mutant Lung Adenocarcinoma Phase 3
Completed NCT02374411 - Knowledge, Attitudes, and Practice of Surgeons Toward Nutrition Support in HIPEC Patients N/A
Completed NCT02454647 - Induction Chemotherapy, Chemoradiotherapy and Surgery in Locally Advanced Gastric Cancer Patients N/A
Completed NCT01579721 - Prospective Randomized Study of SILS Versus CLS for Rectal Cancer Phase 4
Completed NCT01206530 - FOLFOX/Bevacizumab/Hydroxychloroquine (HCQ) in Colorectal Cancer Phase 1/Phase 2
Withdrawn NCT01148082 - School Response to Families Who Have Children With Cancer N/A
Completed NCT00129844 - Study of Motexafin Gadolinium (MGd) for Second Line Treatment of Non-Small-Cell Lung Cancer Phase 2
Completed NCT00377936 - EndoTAG-1 / Gemcitabine Combination Therapy to Treat Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Phase 2
Completed NCT00183859 - Clinical and Pharmacokinetic Trial of Intra-Abdominal Irinotecan Phase 1
Recruiting NCT01930864 - Metformin Plus Irinotecan for Refractory Colorectal Cancer Phase 2
Completed NCT02498860 - Efficacy and Safety of Adjuvant Pemetrexed Plus Cisplatin for Adenocarcinoma of Lung Phase 2
Terminated NCT01441128 - -02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer Phase 1
Active, not recruiting NCT04400474 - Trial of Cabozantinib Plus Atezolizumab in Advanced and Progressive Neoplasms of the Endocrine System. The CABATEN Study Phase 2
Recruiting NCT02133196 - T Cell Receptor Immunotherapy for Patients With Metastatic Non-Small Cell Lung Cancer Phase 2
Completed NCT02875340 - A Study of VAL401 in the Treatment of Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer Phase 2