A randomised phase II/III trial of peri-operative chemotherapy with or without bevacizumab in operable adenocarcinoma of the stomach and gastro-oesophageal junctio
- Conditions
- Cancer of the stomach and gastro-oesophageal junction adenocarcinomaCancer
- Registration Number
- ISRCTN46020948
- Lead Sponsor
- Medical Research Council (UK)
- Brief Summary
2017 results in: https://www.ncbi.nlm.nih.gov/pubmed/28163000 2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31219517 (added 21/06/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 1100
1. Patients with histologically verified gastric or type III gastro-oesophageal junction adenocarcinoma, who have not received any treatment for their cancer
2. Tumours should be stage 1b (T1 N1), II, III with no evidence of distant metastases or stage IV considered to be T4, N1 or N2, M0 where the surgeon believes that an R0 resection can be achieved by excision of a contiguous structure. All patients should have a laparoscopy and a Computed Tomography (CT) of chest and abdomen (pelvis is optional) prior to study entry. Endoscopic UltraSound (EUS) should be performed for all type III gastro-oesophageal junctional tumours and according to local practice for other tumours
Assessments to be performed within four weeks prior to randomisation:
1. World Health Organisation (WHO) performance status zero or one
2. Adequate respiratory function: Forced Expiratory Volume in one second (FEV1) more than 1.5 litres
3. Adequate cardiac ejection fraction more than 50% (as determined by MUltiple Gated Acquisition scan [MUGA] or Echocardiogram [ECHO])
Assessments to be performed within one week prior to randomisation:
1. Adequate bone marrow function:
1.1. Absolute Neutrophil Count (ANC) more than 1.5 litres
1.2. white blood cell count more than 3 x 10^9/l
1.3. platelets more than 100 x 10^9/l
1.4. Haemoglobin (Hb) more than 9 g/dl (can be post-transfusion)
2. Adequate renal function: glomerular filtration rate more than 60 ml/minute (calculated or measured)
3. Adequate liver function:
3.1. serum billirubin 1.5 x Upper Limit of Normal (ULN)
3.2. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) less than or equal to 2.5 x ULN
3.3. Alkaline Phosphatase (ALP) less than or equal to 3 x ULN (in the absence of liver metastases)
4. Proteninuria at baseline less than 1 g of protein/24 hours by a 24-hour urine collection
5. Adequate coagulation profile:
5.1. International Normalised Ratio (INR) less than 1.5 x ULN
5.2. Activated Partial Thromboplastin Time (APTT) less than 1.5 x ULN
6. Patients on oral anticoagulation must change to lower molecular weight heparin prior to randomisation, to be eligible
7. Patient is fit to receive all protocol treatment
8. Completion of baseline quality of life questionnaire
9. No other malignancies within the last four years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix)
10. Women of childbearing potential should have a negative pregnancy test within seven days prior to commencing treatment, or have amenorrhoea for more than two years. Fertile men and women must agree to take adequate contraceptive precautions
Significant co-existing or previous medical conditions:
1. Cerebrovascular disease (including Transient Ischaemic Attacks [TIA] and strokes) within a year before trial entry
2. Cardiovascular diseases as follows:
2.1. Myocardial infarction (less than one year prior to randomisation)
2.2. Uncontrolled hypertension while receiving chronic medication
2.3. Unstable angina
2.4. New York Heart Association (NYHA) grade II or greater congestive heart failure
2.5. Serious cardiac arrhythmia requiring medication
3. Major surgery, major trauma or open biopsy within 28 days prior to study entry
4. Serious non-healing wound, ulcer or bone fracture
5. Evidence of bleeding diathesis or coagulopathy
6. Recent history of any active gastrointestinal inflammatory condition such as peptic ulcer disease. If patients have a known diagnosis of any of the above, evidence of disease control is required negative endoscopy within the past 28 days
Other exclusion factors:
1. Patients with clinically apparent hearing impairment and tinnitus
2. Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication
3. Patients requiring ongoing treatment with contraindicated concomitant medication
4. Patients who have previously received anthracycline treatment
5. Known peripheral neuropathy greater than or equal to grade one (absence of deep tendon reflexes as the sole neurological abnormality does not render the patient ineligible)
6. Known DihydroPyrimidine Dehydrogenase (DPD) deficiency
7. Known allergy to Chinese hamster ovary cell proteins or other recombinant human or humanised antibodies or to any excipients of bevacizumab formulayion, platinum compounds or to any other components of the study drugs
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. Safety, assessed by monitoring gastric perforations, cardiac toxicity, wound healing complications, GastroIntestinal (GI) bleeding and perforations<br> 2. Overall survival<br>
- Secondary Outcome Measures
Name Time Method <br> 1. Treatment-related morbidity<br> 2. Response rates to pre-operative treatment<br> 3. Surgical resection rates<br> 4. Disease-free survival<br> 5. Quality of life<br> 6. Cost-effectiveness<br>