Locally advanced rectal cancer MedDRA version: 14.1 Level: PT Classification code 10038049 Term: Rectal cancer stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10038050 Term: Rectal cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 1+ or urine protein/creatinine ratio =1.0, 24-hour urine protein should be obtained and the level must be =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: • 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question is to see how effective the two different treatment arms are. Efficacy will be measured by examining tissue removed at surgery to see how many patients have a pathological complete response; that is - how many patients do not have any visible tumour left, even when looking through a microscope.;Secondary Objective: We will look at other measures of efficacy inculding: How many patients' tumours shrink (response rate), in how many patients can the tumour be completely removed (circumerential resection margin (CRM) negative resection rate), how long does it take before a patient's cancer begins to get worse (progression free survival), and how long do the patients survive (overall survival)? We will also look at side effects of the treatments (adverse events), and how many patients have a colostomy one year after treatment (colostomy rate). ;Primary end point(s): The primary endpoint for this trial is the pathological complete response (pCR) rate. The proportion of patients in each arm who achieve a pCR will be presented, along with a 95% CI. ;Timepoint(s) of evaluation of this end point: The pCR rate will be assessed after surgery. Within each group the achieved pCR rate will be compared to the rate achieved by radiotherapy alone (5%). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • RECIST response rate • CRM negative resection rate • T and N stage downstaging • Progression free survival (PFS) • Disease free survival (DFS) • Overall Survival (OS) • Local control 1 year colostomy rate • Adverse events • Compliance of chemotherapy treatment • Tumour Regression Grade (TRG) • Tumour Cell Density (TCD);Timepoint(s) of evaluation of this end point: • RECIST response rate: pre-cycle 4 & post end of chemotherapy • CRM negative resection rate: post surgery • T and N stage downstaging: post end of chemotherapy • Progression-free survival: disease progression or death • Disease-free survival: from surgery to occurrence of relapse, second primary or death from any cause • Overall survival: study entry until death • Local control: patients with CRM -ve resection - surgery until local failure • 1-year colostomy rate: 1 year post surgery • Adverse events: baseline, during/after treatment, surgery & follow up • Chemotherapy compliance: dose reductions & delays to all chemotherapy agents during treatment • Tumour Regression Grade: post surgery • Tumour Cell Density: post surgery | — |
Countries
United Kingdom
Contacts
Public ContactNatasha Hava
University College London
Outcome results
None listed