This is a phase II, randomised trial of combination chemotherapy with bevacizumab for patients with high risk but surgically resectable cancer of the rectum to be recruited by multiple UK sites
- Conditions
- ocally advanced rectal cancerMedDRA version: 14.1Level: PTClassification code 10038049Term: Rectal cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 14.1Level: PTClassification code 10038050Term: Rectal cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2010-022754-17-GB
- Lead Sponsor
- niversity College London
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
• Histologically confirmed diagnosis of adenocarcinoma of the rectum
• Distal part of the tumour within 4–12 cm of the anal verge
• No unequivocal evidence of established metastatic disease (on chest/abdominal/pelvis CT). Patients with equivocal lesions (as determined at MDT) are eligible
• MRI-evaluated locally advanced tumour:
• T3b, T3c or T3d and N0–N2
• OR presence of macroscopic extramural venous invasion (V2 disease)
• AND T3 tumour must be =2mm from the mesorectal
• Measurable disease (using RECIST criteria, v1.1)
• WHO performance status 0 or 1
• In the opinion of the investigator:
• General condition considered suitable for radical pelvic surgery
• Candidate for systemic therapy with FOLFOX/FOLFOXIRI plus bevacizumab
• Adequate bone marrow, hepatic and renal function:
• Haemoglobin =8.0 g/dL
• ANC =2 x 10^9/L
• Platelet count =100 x 10^9/L
• ALT or AST =1.5 x ULN (upper limit of normal)
• ALP =1.5 x ULN
• Total bilirubin =1.5 x ULN
• Serum creatinine =1.5 x ULN
• Creatinine clearance =50 mL/min using the Cockroft–Gault formula.
If the calculated GFR is below <50 ml/min, GFR should be assessed using
51Cr-EDTA or 99mTc-DTPA method to confirm GFR is =50 ml/min
• INR = 1.1
• Urine protein =1 with dipstick or urine analysis. For proteinuria >1+ or urine protein/creatinine ratio =1.0, 24-hour urine protein should be obtained and the level must be <2g for eligibility
• No evidence of established or acute ischaemic heart disease on ECG and normal clinical cardiovascular assessment
• No known significant impairment of intestinal absorption
• At least 18 years of age, but not more than 70 years
• Willing and able to give informed consent, comply with treatment and follow up schedule
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
• Primary tumour or lymph node on MRI extending =1mm from, or breaching the circumferential resection margin
• Disease outside of the mesorectal envelope (internal iliac/ lateral pelvic lymph node)
• Clinically significant cardiovascular or coronary disease (including myocardial infarction, angina (stable or unstable), symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) =2 years before randomisation
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• History of an arterial thromboembolic event during the previous 2 years. This includes myocardial infarction (MI), transient ischaemic attack (TIA), cerebrovascular accident (CVA), symptomatic peripheral vascular disease or other relevant history in the opinion of the investigator
• Evidence of bleeding problems or coagulopathy
• Significant and continuing rectal bleeding leading to a haemoglobin <8 g/dL
• Patients receiving warfarin/coumarin derived anticoagulants at full therapeutic doses are excluded, but prophylactic doses of 1 mg to prevent Hickman line clotting are eligible
• Chronic use of aspirin (>325 mg/day) or clopidrogel (>75 mg/day) within 10 days of first planned study treatment
• Require regular use of anti-diarrhoeal (i.e. daily use of loperimide)
• Serious uncontrolled intercurrent illness including poorly controlled diabetes mellitus
• Known hypersensitivity to any of the study drugs
• Serious wound, ulcer or bone fracture
• Current or impending rectal obstruction
• Metallic colonic or rectal stent in situ
• patietns with ileostomy will not be able to participate IF they require
regular use of anti-diarrhoeal medication
• Previous pelvic radiotherapy
• Previous intolerance to fluoropyrimidine chemotherapy
• Previous treatment with bisphosphonates
• Infectious illness requiring antibiotics within 1 week of randomisation
• Previous treatment with another investigational agent within 30 days prior to randomisation
• Patients with a history of previous malignancy in the past 5 years, excepting basocellular or squamous cell skin cancer, or properly treated cervicouterine cancer in situ
• Known HIV, HBV or HCV infection
• Current smoker, or clinically relevant history of drug or alcohol abuse
• Pregnant or lactating women or pre menopausal women not using adequate contraception. Men and women of child-bearing potential must use adequate contraception
• Patients with any other condition or concurrent medical or psychiatric disease who, in the opinion of the investigator, is not eligible to enter the study
• Inability or unwillingness to comply with the protocol
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