A double-blind, randomised, 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 - AVAGAST
- Conditions
- Adult and elderly patients with histologically confirmed, inoperable, locally advanced or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction, who have received no prior treatment for advanced or metastatic gastric cancer.MedDRA version: 9.1 Level: LLT Classification code 10063916 Term: Metastatic gastric cancer
- Registration Number
- EUCTR2007-000175-42-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 774
1. Written informed consent (informed consent document to be approved by the institution’s Independent Ethics Committee/Institutional Review Board (IEC/IRB)) obtained prior to any study specific procedures.
2. Age = 18 years.
3. ECOG PS of 0, 1 or 2.
4. Life expectancy of at least 3 months.
5. Able to comply with the protocol.
6. Histologically confirmed adenocarcinoma of the stomach or gastro-oesophageal junction* with inoperable, locally advanced or metastatic disease, not amenable to curative therapy.
*Adenocarcinoma of gastro-oesophageal junction (GOJ) is defined as tumours that have their centre within 5 cm proximal and distal of the anatomical cardia as described in Siewert’s classification system.
7. Measurable disease or non measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumours (RECIST). Patients with peritoneal disease would generally be regarded as having evaluable disease and allowed to enter the trial.
8. Patient not receiving anticoagulant medication must have an INR = 1.5 and aPTT =1.5 x ULN within 7 days prior to randomisation*.
*The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomisation.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. 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.
2. Previous platinum or anti-angiogenic therapy.
3. Patients with locally advanced disease who are candidates for curative therapy.
4. Radiotherapy within 28 days of randomisation.
5. 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).
6. Minor surgical procedures within 2 days prior to randomisation (including CVAD placement for chemotherapy administration).
7. Evidence of CNS metastasis at baseline.
8. History or evidence upon physical/neurological examination of CNS disease unrelated to cancer unless adequately treated with standard medical therapy.
9. History of another malignancy which could affect compliance with the protocol or interpretation of results. Patients are generally eligible if they have had non-melanomatous cancer of the skin, carcinoma in situ of the cervix, or another malignancy treated with curative intent if they have been disease-free for more than 5 years.
10. Inadequate bone marrow function: ANC < 1.5 x 1000,000,000/L, platelet count < 100 x 1000,000,000/L or Hb < 9 g/dL.
11. Inadequate liver function: serum (total) bilirubin > 1.5 x ULN, AST & ALT > 2.5 x ULN (> 5 x ULN in patients with liver metastases), alkaline phosphatase > 2.5 x ULN or > 5 x ULN in case of liver metastases or > 10 x ULN in case of bone metastases.
12. Inadequate renal function:
• Creatinine clearance should be =60 ml/min. Patients with a creatinine clearance just below 60 ml/min may be eligible if a measured creatinine clearance (based on 24 hour urine collection or other reliable method) is =60 ml/min.
• Urine dipstick for proteinuria < 2+. Patients with = 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate < 1 g of protein/24 hr.
13. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents (= 6 months prior to randomisation), myocardial infarction (= 6 months prior to randomisation), unstable angina, New York Heart Association (NYHA Appendix 5) Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment.
14. Active infection requiring intravenous antibiotics at randomisation.
15. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
16. Serious or non-healing wound, peptic ulcer, or (incompletely healed) bone fracture.
17. Active gastrointestinal bleeding.
18. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of randomisation.
19. Neuropathy (e.g. impairment of hearing and balance) = grade II according to Common Terminology Criteria for Adverse Events v3.0.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method