A two-arm phase II randomised trial of intermittent chemotherapy plus continuous cetuximab and of intermittent chemotherapy plus intermittent cetuximab in first line treatment of patients with K-ras-normal (wild-type) metastatic colorectal cancer
- Conditions
- Metastatic colorectal cancerCancerColorectal cancer
- Registration Number
- ISRCTN38375681
- Lead Sponsor
- Medical Research Council (MRC) (UK)
- Brief Summary
2014 Results article in http://www.ncbi.nlm.nih.gov/pubmed/24703531 results
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 130
Amended as of 17/02/2009:
1. Written informed consent
2. Consent for screening of an archival formalin-fixed paraffin embedded (FFPE) tumour block for determination of K-ras status, with only patients with only K-raswt tumours being eligible for randomisation
3. Once K-raswt status confirmed, written informed consent for participation in the trial
4. Patients at least 18 years or over, either sex
5. Confirmed colorectal adenocarcinoma:
5.1. 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
5.2. Histologically/cytologically-confirmed metastatic adenocarcinoma, together with clinical and/or radiological evidence of colorectal primary tumour
6. Inoperable metastatic or locoregional disease
7. Patients with potentially resectable liver metastases are eligible (see exclusion criteria)
8. Unidimensionally measurable disease (Response Evaluation Criteria in Solid Tumours [RECIST] criteria). Baseline computed tomography (CT) scan must be performed within 4 weeks prior to treatment
9. No previous systemic palliative chemotherapy for metastatic disease
10. Adjuvant chemotherapy with 5FU +/- FA, capecitabine or irinotecan may have been given, if completed greater than 1 month prior to trial entry
11. Chemoradiotherapy with 5FU +/- FA or capecitabine for rectal cancer may have been given, if completed greater than 1 month prior to trial entry
12. World Health Organization (WHO) performance status (PS) 0, 1 or 2 and considered by responsible consultant to be fit to undergo combination chemotherapy
13. Baseline laboratory tests (within 1 week prior to randomisation):
13.1. Neutrophils greater than or equal to 1.5 x 10^9/l and platelet count greater than or equal to 100 x 10^9/l
13.2. Serum bilirubin less than or equal to 1.25 x upper limit of normal (ULN), alkaline phosphatase less than or equal to 5 x ULN, and serum transaminase (either aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) less than or equal to 2.5 x ULN
13.3. Estimated creatinine clearance (Cockcroft and Gault) greater than or equal to 50 ml/min or measured glomerular filtration rate (GFR) (ethylenediaminetetraacetic acid [EDTA] clearance) greater than or equal to 50 ml/min
14. For women of childbearing potential, negative pregnancy test and adequate contraceptive precautions
15. Effective contraception for male patients if the risk of conception exists
16. Written informed consent to allow pathological material to be analysed for estimated glomerular filtration rate (EGFR) status, even if this is already known
Initial information at time of registration:
1. Patients at least 18 years or over
2. Confirmed colorectal adenocarcinoma:
2.1. Previous or current histologically-confirmed primary adenocarcinoma of colon or rectum, together with clinical or radiological evidence of current advanced and/or metastatic disease
2.2. Histologically/cytologically-confirmed metastatic adenocarcinoma, together with cli
Amended as of 17/02/2009:
1. Patients who have a confirmed K-ras mutation in their tumour post screening
2. Patients who are receiving combination chemotherapy prior to the planned resection of operable liver metastases (defined as less than 4 unilobar liver metastases, each less than 4 cm in size and without major vascular involvement). Patients outside these criteria are of uncertain operability and are eligible.
3. Patients who have received any prior chemotherapy with oxaliplatin
4. Patients who are unfit for the chemotherapy regimens in this protocol, e.g.:
4.1. Severe uncontrolled concurrent medical illness (including poorly controlled angina or very recent myocardial infarction [MI], i.e. in previous 12 weeks) likely to interfere with protocol treatments
4.2. 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
4.3. Partial or complete bowel obstruction
4.4. Pre-existing neuropathy (greater than Grade 1)
5. Patients requiring ongoing treatment with a contraindicated concomitant
6. 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
7. Patients with known hypersensitivity reactions to any of the components of the study treatments
8. Patients with brain metastases
9. Patients with a personal or family history of dihydropyrimidine dehydrogenase (DPD) deficiency, or with proven DPD deficiency
Initial information at time of registration:
1. Patients who are receiving combination chemotherapy prior to the planned resection of operable liver metastases (defined as less than four unilobar liver metastases, each less than 4 cm in size and without major vascular involvement). Patients outside these criteria are of uncertain operability and are eligible
2. Patients who have received any prior chemotherapy with oxaliplatin
3. Patients who are unfit for the chemotherapy regimens in this protocol, e.g.:
3.1. Severe uncontrolled concurrent medical illness (including poorly controlled angina or very recent Myocardial Infarction (MI), i.e. in previous 12 weeks) likely to interfere with protocol treatments
3.2. 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
3.3. Partial or complete bowel obstruction
3.4. Pre-existing neuropathy (more than Grade one)
4. Patients requiring ongoing treatment with a contraindicated concomitant medication
5. 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
6. Patients with known hypersensitivity reactions to any of the components of the study treatments
7. Patients with brain metastases
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Failure-free survival at ten months.
- Secondary Outcome Measures
Name Time Method <br> Amended as of 17/02/2009:<br> 1. To assess the safety of cetuximab reintroduction with regards to frequency of Grade 3 and 4 allergic reactions<br> 2. 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> 3. Quality of life<br><br> Initial information at time of registration:<br> 1. To assess the safety of cetuximab reintroduction with regards to frequency of grade three and four allergic reactions<br> 2. 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, and compare these outcomes in an indirect comparison with the main COIN arms<br>