Identifying biomarkers to predict clinical benefit in patients with colorectal cancer treated with bevacizumab
- Conditions
- Metastatic colorectal cancerCancerMalignant neoplasm of rectosigmoid junction
- Registration Number
- ISRCTN97323814
- Lead Sponsor
- The Christie NHS Foundation Trust (UK)
- Brief Summary
1. 2018 results in https://www.ncbi.nlm.nih.gov/pubmed/30405103 (added 31/01/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 70
1. Aged greater than or equal to 18 years old, either sex
2. Signed informed consent and ability to comply with study protocol
3. Histologically confirmed colorectal cancer.
4. Previously untreated metastatic disease
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
6. Life expectancy greater than 12 weeks
7. Adequate bone marrow function: absolute neutrophil count (ANC) more than 1.5 x 10^9/L; platelets more than or equal to 100 x 10^9/L; haemoglobin (Hb) more than or equal to 9 g/dL (can be post-transfusion)
8. International normalised ratio (INR) less than or equal to 1.5 and activited partial thromboplastin time (aPTT) less than or equal to 1.5 x upper limit of normal (ULN) within 7 days prior to starting study treatment
9. Adequate liver function: serum bilirubin less than or equal to 1.5 x ULN except in case of known Gilbert syndrome; transaminases less than or equal to 2.5 x ULN in the absence of liver metastases or less than or equal to 5 x ULN in the presence of liver metastases
10. Adequate renal function: estimated glomerular filtration rate greater than or equal to 50 ml/min by the Wright Formula
11. Urine dipstick for proteinuria less than or equal to 2+. If urine dipstick is more than or equal to 2+, a 24-hour urine must demonstrate less than 1 g of protein in 24 hours
12. At least one metastatic deposit in the abdomen (including inguinal lymphadenopathy) liver, retroperitoneum, pelvis or thorax greater than or equal to 3 cm diameter
13. No contraindications to magnetic resonance imaging (MRI) scanning or allergy to gadolininum-containing contrast media
1. Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab
2. Significant traumatic injury or radiotherapy during 4 weeks preceding potential first dose of bevacizumab
3. Adjuvant therapy within the previous 12 months
4. Patients with previous adjuvant exposure to oxaliplatin can only take part if it is more than 12 months since their last exposure to oxaliplatin and they have grade I or less, residual peripheral neuropathy
5. No previous exposure to VEGF inhibitors in the adjuvant setting
6. History or evidence upon physical examination of brain metastases. Evidence of spinal cord compression. Computed tomography (CT)/MRI of the brain is mandatory (within 4 weeks prior to randomisation) in case of clinical evidence of brain metastases.
7. Pregnant or breast-feeding women. Positive pregnancy test (serum or urine beta-human chorionic gonadotropin [ß-HCG]) for women of reproductive potential
8. Fertile woman of childbearing potential not using adequate contraception (oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
9. Other malignancies within 5 years prior to randomisation, except for adequately treated carcinoma in situ of the cervix and/or basal cell skin cancer
10. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this trial
11. Known hypersensitivity to bevacizumab, 5-fluorouracil, capecitabine, oxaliplatin or irinotecan
12. Known dihydro-pyrimidine dehydrogenase deficiency
13. Non-healing wound, ulcer or bone fracture
14. Patients cannot enter the trial if they have developed a deep venous thrombosis (DVT) or commenced therapeutic anticoagulation for any other reason, e.g., atrial fibrillation (AF) within the 4 weeks preceding the trial. Patients with a known DVT or AF on stable therapeutic doses of low molecular weight heparin for greater than 4 weeks duration, can enter the trial.
15. Patients with haemorrhagic disorders
16. Poorly controlled hypertension (sustained blood pressure [BP] greater than 150/100 mmHg despite antihypertensive therapy
17. Previous cerebrovascular accident (CVA), transient ischaemic attack (TIA) or subarachnoid haemorrhage (SAH) within six months before trial entry
18. Clinically significant cardiovascular disease, for example:
18.1. Myocardial infarction or unstable angina within 6 months of trial entry
18.2. New York Heart Association (NYHA) grade 2 or worse congestive heart failure (CHF)
18.3. Poorly controlled cardiac arrhythmia despite medication
19. Current or recent (within 10 days prior to first dose of trial treatment) use of aspirin greater than or equal to 325 mg/day
20. Pre-existing sensory or motor neuropathy greater than or equal to grade 2, uncontrolled spinal cord compression, or
21. Carcinomatous meningitis or new evidence of brain or leptomeningeal disease
22. Predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline of greater than 3 loose stools
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method