{"registry": "ISRCTN", "registryId": "ISRCTN27286448", "source": "https://www.isrctn.com/ISRCTN27286448", "apiSource": "https://www.isrctn.com/api/trial/ISRCTN27286448/format/default", "fetchedAt": "2026-10-07T17:01:19.422177Z", "license": "CC BY 4.0", "licenseSource": "https://www.isrctn.com/page/faqs#licence-to-post", "study": {"title": "A Phase III trial comparing either COntinuous chemotherapy plus cetuximab or INtermittent chemotherapy with standard continuous palliative combination chemotherapy with oxaliplatin and a fluoropyrimidine in first line treatment of metastatic colorectal cancer", "scientificTitle": "A Phase III trial comparing either COntinuous chemotherapy plus cetuximab or INtermittent chemotherapy with standard continuous palliative combination chemotherapy with oxaliplatin and a fluoropyrimidine in first line treatment of metastatic colorectal cancer", "acronym": "COIN", "hypothesis": "This randomized phase III trial is studying combination chemotherapy and cetuximab to see how well they work compared to combination chemotherapy alone as first-line therapy in treating patients with metastatic colorectal cancer.\n\nMore details can be found at: http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=10", "primaryOutcome": "Not provided at time of registration.", "secondaryOutcome": "Not provided at time of registration.", "intervention": "\n\tChemotherapy\nThe Oxaliplatin regimens used in the trial can be selected on a per patient basis, but prior to knowledge of the treatment randomisation. This conforms with the NICE guidance regarding allowing patient choice with respect to oral or intravenous (IV) therapy. Some centres may be subject to practical constraints such that only one of the regimens will be feasible. In this case the centre may make a policy that all patients treated in that centre will receive one or other regimen. There is no data yet to indicate that one regimen is superior to the other. The regimen will be either:\nOxMdG: a combination of folinic acid (200 mg/m^2 IV over 2 h), concurrent administration of Oxaliplatin (85 mg/m^2 IV over 2 h) plus bolus 5FU (400 mg/m^2) followed by a 46 hour IV infusion of 5FU 2400 mg/m^2 repeated every 2 weeks.\nor:\nXELOX: a combination of Capecitabine plus Oxaliplatin: Oxaliplatin 130 mg/m^2 IV over 2 hours day 1, plus Capecitabine 1000 mg/m^2 twice a day (bd), orally (po) days 1-14 repeated 3 weekly.\n\nTreatment duration and breaks\nArm A:\nContinuous chemotherapy (Control Arm): These patients will continue the\nchemotherapy regimen (with dose reductions as required) until progressive disease \nis identified on radiological grounds (RECIST), or the development of cumulative \ntoxicity or because of patient choice to stop chemotherapy. Patients in this arm should continue on treatment with no more than a three week interval off treatment for any reason. The cumulative toxicity that is most likely to occur is the neuropathy associated with Oxaliplatin, which increases in incidence from about 7 months duration of therapy. If this occurs, patients may continue on the fluoropyrimidine component of the regimen with dose increment until evidence of disease progression. If the neuropathy resolves to < grade 1 the Oxaliplatin may be reintroduced cautiously at the investigator's discretion. These patients will be evaluated with 12 weekly computed tomography (CT) scans to assess radiological evidence of progression.\n\nArm B:\nContinuous chemotherapy plus Cetuximab: These patients will continue chemotherapy plus Cetuximab as Arm A above.   Cetuximab will be continued if chemotherapy is stopped because of toxicity or patient choice, but should be discontinued on evidence of disease progression or unacceptable Cetuximab toxicity. These patients will be evaluated with 12 weekly CT scans to assess radiological evidence of progression.\n\nArm C:\nIntermittent chemotherapy: These patients will be treated for 12 weeks. Chemotherapy will then stop and they will be monitored clinically, at least 6 weekly, and with CT scans at 12 weekly intervals. On evidence of progression of disease using RECIST criteria or on clinical evidence of deterioration, the same chemotherapy will be restarted, for a further 12 weeks course. At that point treatment will again be interrupted. Patients with chemo-sensitive disease may have an unlimited number of 12-week treatments alternating with treatment breaks. When the patient demonstrates resistance to this treatment as evidenced by progressive disease during a period on chemotherapy or clinical choice, they will move on to second-line therapy or supportive care.\n\tDrug\n\tPhase III\n\tVarious\n      ", "condition": "\n\tMetastatic colorectal cancer\n\tCancer\n\tColorectal\n      ", "studyDesign": "Randomised controlled trial", "overallEndDate": "2005-08-01T00:00:00.000Z", "clinicalTrialsGovNumber": "NCT00182715", "lastUpdated": "2018-10-19T11:51:39.856Z", "eligibility": {"inclusion": "1. Confirmed colorectal adenocarcinoma:\n- either previous or current histologically confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of advanced and/or metastatic disease\n- or histologically/cytologically confirmed metastatic adenocarcinoma, together with clinical and/or radiological evidence of colorectal primary tumour\n2. Inoperable metastatic or locoregional disease. Patients who are currently eligible for combination first-line chemotherapy prior to liver resection under National Institute for Clinical Excellence (NICE) guidance are ineligible for this study.\n3. Unidimensionally measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST])\n4. No previous systemic palliative chemotherapy for metastatic disease\n5. Adjuvant chemotherapy with 5-Fluorouracil (5FU) +/- folinic acid (FA), Capecitabine or irinotecan may have been given, if completed >6 months prior to trial entry\n6. Rectal chemoradiotherapy with 5FU +/- FA may have been given, if completed >1 month prior to trial entry\n7. World Health Organistion (WHO) performance status (PS) 0, 1 or 2 and considered by responsible consultant to be fit to undergo combination chemotherapy\n8. Baseline laboratory tests (within 1 week prior to randomisation):\nWhite blood cell count (WBC) ≥4 x 10^9/l, neutrophils ≥1.5 x 10^9/l and platelet count >150 x 10^9/l.\nSerum bilirubin ≤1.25 x upper limit of normal (ULN), alkaline phosphatase ≤5 x ULN, and serum transaminase (either aspartate transaminase [AST] or alanine transaminase [ALT]) ≤3 x ULN.\nEstimated creatinine clearance >50 ml/min or measured glomerular filtration rate (GFR) (ethylene diamine tetraacetic acid [EDTA] clearance) >50 ml/min.\n9. For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions\n10. Consent to allow surplus pathological material to be analysed for epidermal growth factor receptor (EGFR) testing", "exclusion": "1. Patients who are unfit for the chemotherapy regimens in this protocol e.g.\nSevere uncontrolled concurrent medical illness (including poorly-controlled angina or very recent myocardial infarction [MI], i.e. in previous 3 months) likely to interfere with protocol treatments\nAny psychiatric or neurological condition which is felt likely to compromise the patient's ability to give informed consent or to comply with oral medication\nPartial or complete bowel obstruction\nPre-existing neuropathy (>grade 1)\n2. Patients requiring ongoing treatment with a contraindicated concomitant medication\n3. Patients with another previous or current malignant disease which, in the judgement of the treating investigator, is likely to interfere with COIN treatment or assessment of response", "ageRange": "Not Specified", "gender": "All", "participantType": "Patient"}, "recruitment": {"recruitmentStart": "2003-08-01T00:00:00.000Z", "recruitmentEnd": "2005-08-01T00:00:00.000Z", "recruitmentStatusOverride": "", "recruitmentStartStatusOverride": "", "targetEnrolment": "2421", "totalFinalEnrolment": ""}, "countries": ["United Kingdom", "Wales"], "locations": [{"name": "Wales Cancer Network Co-ordinating Office", "city": "Cardiff", "state": "", "country": "United Kingdom", "zip": "CF4 7XL"}], "sponsors": [{"organisation": "Medical Research Council (UK)", "sponsorType": "Research council", "rorId": "https://ror.org/03x94j517"}], "funders": [{"name": "The trial is funded by Cancer Research UK and Medical Research Council (MRC), via the Clinical Trials Advisory and Awards Committee (CTAAC). The CRUK grant award reference number is C1210-A4528"}]}, "studySha256": "4c84c22a31aa5b17fc0c401705a3fd4dff14cb9bf3a784a09b5293db7b60da88"}