A Study of Bevacizumab in Combination With Capecitabine and Cisplatin as First-line Therapy in Patients With Advanced Gastric Cancer
Condition: Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Bevacizumab; Capecitabine; Cisplatin; Placebo; 5-fluorouracil
Intervention description: Intravenous bevacizumab 7.5 mg/kg once every 3 weeks, given until disease progression or unmanageable toxicity.; Oral capecitabine 1,000 mg/m˄2 twice daily for 14 days every 3 weeks, given until disease progression or unmanageable toxicity.; 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.; Intravenous placebo every 3 weeks, given until disease progression or unmanageable toxicity.; 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.
Intervention MeSH terms: Bevacizumab; Capecitabine; Fluorouracil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 774.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Avastin; Metastatic Adenocarcinoma; AVAGAST

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.
    

Eligibility criteria:

        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.