Bevacizumab And Combination Chemotherapy in Rectal Cancer Until Surgery

• Status: Completed
• Trial end date: 2019-02-14
• Target enrollment: 0
• Participant gender: 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 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College, London
• Collaborators: Cancer Research UK; Hoffmann-La Roche
• Treatments: 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