A two-arm randomised trial of intermittent chemotherapy plus continuous cetuximab and of intermittent chemotherapy plus intermittent cetuximab in first line treatment of metastatic colorectal cancer - COIN-B

Phase 1

• Conditions: Metastatic Colorectal Cancer; MedDRA version: 14.1 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2006-003049-17-GB
• Lead Sponsor: Medical Research Council

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-12-17
• Study Completion: 2016-01-18
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 169

Inclusion Criteria

• Written informed consent
• Consent for screening of an archival FFPE tumour block for determination of K-ras status, with only patients with only K-raswt tumours being eligible for randomisation
• Once K-raswt status confirmed, written informed consent for participation in the trial
• Patients at least 18 years or over.
• Confirmed colorectal adenocarcinoma:
- Either previous or current histologically-confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of current advanced and / or metastatic disease.
- Or histologically/cytologically-confirmed metastatic adenocarcinoma, together with clinical and/or radiological evidence of colorectal primary tumour.
• Inoperable metastatic or locoregional disease.
• Patients with potentially resectable liver metastases are eligible (see exclusion criteria).
• Unidimensionally measurable disease (RECIST criteria, see Appendix VIII – RECIST Response Definitions). Baseline CT scan must be performed within 4 weeks prior to treatment.
• No previous systemic palliative chemotherapy for metastatic disease.
• Adjuvant chemotherapy with 5FU +/- FA, capecitabine or irinotecan may have been given, if completed > 1 month prior to trial entry.
• Chemoradiotherapy with 5FU +/- FA or capecitabine for rectal cancer may have been given, if completed > 1 month prior to trial entry.
• WHO performance status (PS) 0, 1 or 2 (see Appendix VII – WHO Performance Status) and considered by responsible consultant to be fit to undergo combination chemotherapy.
• Baseline laboratory tests (within 1 week prior to randomisation):
- Neutrophils = 1.5 x109/l and platelet count = 100 x109/l.
- Serum bilirubin = 1.25 x upper limit of normal (ULN), alkaline phosphatase = 5 x ULN, and serum transaminase (either AST or ALT) = 2.5 x ULN.
- Estimated creatinine clearance (Cockcroft and Gault; Appendix V – Cockcroft and Gault Formula) =50ml/min or measured GFR (EDTA clearance) =50 ml/min.
• For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions.
• Effective contraception for male patients if the risk of conception exists.
• Written informed consent to allow pathological material to be analysed for EGFR status, even if this is already known.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Patients who have a confirmed K-ras mutation in their tumour post screening
• Patients who are receiving combination chemotherapy prior to the planned resection of operable liver metastases (defined as less than 4 unilobar liver metastases, each <4cm in size and without major vascular involvement). Patients outside these criteria are of uncertain operability and are eligible.
• Patients who have received any prior chemotherapy with oxaliplatin.
• Patients who are unfit for the chemotherapy regimens in this protocol, e.g.:
- Severe uncontrolled concurrent medical illness (including poorly controlled angina or very recent MI, i.e. in previous 12 weeks) likely to interfere with protocol treatments.
- Any psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication.
- Partial or complete bowel obstruction.
- Pre-existing neuropathy (> Grade 1).
• Patients requiring ongoing treatment with a contraindicated concomitant medication
• Patients with another previous or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with COIN-B treatment or assessment of response.
• Patients with known hypersensitivity reactions to any of the components of the study treatments.
• Patients with brain metastases.
• Patients with a personal or family history of DPD deficiency, or with proven DPD deficiency.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary aim of the COIN-B trial is to determine whether adding cetuximab to intermittent OxFp chemotherapy in tumours with K-raswt status, is active, safe and feasible, with the primary outcome measure of failure-free survival at 10 months.;<br> Secondary Objective: The secondary aims are:<br> - To assess the safety of cetuximab reintroduction with regards to frequency of Grade 3&4 allergic reactions.<br> - To evaluate whether either arm will result in improved disease control (CR+PR+SD) at 24 weeks, overall survival, progression-free survival, response rates at 12, 24 and 36 weeks and toxicity.<br> - Quality of life<br> ;<br> Primary end point(s): The primary outcome measure is to determine whether adding cetuximab to intermittent OxFp chemotherapy in tumours with K-raswt status, is active, safe and feasible, with the primary outcome measure of failure-free survival at 10 months.<br>