Overview
Bevacizumab And Combination Chemotherapy in Rectal Cancer Until Surgery
Status:
Completed
Completed
Trial end date:
2019-02-14
2019-02-14
Target enrollment:
0
0
Participant gender:
All
All
Summary
The purpose of this study is to evaluate the efficacy, toxicity and feasibility of FOLFOX/ bevacizumab and FOLFOXIRI/ bevacizumab neoadjuvant therapy in poor prognosis rectal cancer as defined by MRI.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
University College, LondonCollaborators:
Cancer Research UK
Hoffmann-La RocheTreatments:
Bevacizumab
Fluorouracil
Irinotecan
Oxaliplatin
Criteria
Inclusion- 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 with the following:
- T3 tumours extending (≥ 4 mm), beyond the muscularis propria N0-N2
- Or tumours (involving or threatening the peritoneal surface)
- OR presence of macroscopic extramural venous invasion (V2 disease)
- AND for tumours below the peritoneal reflection, the primary tumour or involved lymph
node (on MRI) must be >1 mm from the mesorectal fascia
- Measurable disease (using RECIST criteria v1.1)
- WHO performance status 0 - 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 ≥80 g/L
- ANC ≥2 x 109/L
- Platelet count ≥100 x 109/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 Cockcroft-Gault formula
- INR ≤ 1.1
- Urine protein ≤1+ with dipstick or urine analysis
- For proteinuria ≥2+ or urine protein/creatinine ratio ≥ 1.0, 24-h urine protein
should be obtained and the level must be ≤2 g 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 75 years
- Willing and able to give informed consent, comply with treatment and follow up
schedule
Exclusion
- Disease outside of the mesorectal envelope (internal iliac/lateral pelvic lymph node)
- Clinically significant cardiovascular or coronary disease <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
- 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 1mg to prevent Hickman line clotting are
eligible
- Chronic use of aspirin (>325 mg/day) or clopidogrel (>75 mg/day) within 10 days of
first planned study treatment
- Require regular use of anti-diarrhoeal (e.g. daily use of loperamide)
- 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
- 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