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21 March 2013
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| [ Print-friendly version ] |
| A randomised trial assessing the role of two new agents in the management of advanced colorectal cancer |
| ISRCTN | ISRCTN79877428 |
| DOI | 10.1186/ISRCTN79877428 |
| ClinicalTrials.gov identifier | NCT00008060 |
| EudraCT number | |
| Public title | A randomised trial assessing the role of two new agents in the management of advanced colorectal cancer |
| Scientific title | |
| Acronym | MRC FOCUS (Fluorouracil, Oxaliplatin, CPT-11, Use and Sequencing) |
| Serial number at source | E164/3; CR08 |
| Study hypothesis |
1. The principal objective is to determine whether there is an advantage for patients for the use of combination chemotherapy for colorectal cancer compared with the standard approach of sequential single-agent therapies.
2. In addition the trial will determine whether combination therapy is best used in first-line management of advanced disease, or reserved for second-line treatment following standard first-line single-agent modified de Gramont (MdG). 3. Finally, the trial will compare the efficacy and toxicity of an irinotecan-containing combination versus the equivalent oxaliplatin-containing combination. |
| Lay summary | |
| Ethics approval | Added 17/07/2007: Northern and Yorkshire Medical Research Ethics Committee, approval given on 12/11/1999. |
| Study design | Randomised controlled trial |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Colorectal cancer |
| Participants - inclusion criteria |
1. Histologically confirmed adenocarcinoma of the colon or rectum
2. Inoperable disease (either locally advanced, recurrent or metastatic and not suitable for curative surgery or radiotherapy) 3. Measurable or evaluable disease 4. World Health Organization (WHO) performance status zero to two 5. Fit, able and willing to undergo any of the possible trial treatments and to comply with the quality of life questionnaires |
| Participants - exclusion criteria |
1. White Blood Cells (WBC) less than 4 x 10^9/l
2. Platelets less than 150 x 10^9/l 3. Bilirubin more than 1.25 x Upper Limit of Normal (ULN) 4. Alkaline phosphatase more than 3 x ULN 5. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) more than 3 x ULN 6. Renal impairment (calculated Creatinine Clearance [CrCl] less than 60 ml/min, or measured Glomerular Filtration Rate [GFR] below normal range) 7. Serious uncontrolled medical co-morbidity |
| Anticipated start date | 12/05/2000 |
| Anticipated end date | 31/12/2003 |
| Status of trial | Completed |
| Patient information material | |
| Target number of participants | 700 in arm one and 350 each in other arms |
| Interventions |
This is a five-arm trial in which patients will be randomly allocated to one of five 'treatment plans'. These plans comprise first-line and, in some cases, a second-line chemotherapy treatment plan. The five plans are:
Plan A: First-line Modified de Gramont (MdG) regimen. In the event of radiological or clinical disease progression, MdG will be stopped, and, if appropriate, patients will receive second-line therapy with single-agent irinotecan. Plan B: First-line MdG. In the event of radiological or clinical progression patients will, if appropriate, receive second-line therapy with MdG-plus-Irinotecan (IrMdG). Plan C: First-line treatment with IrMdG. Plan D: First-line MdG. In the event of radiological or clinical progression patients will, if appropriate, receive second-line therapy with MdG-plus-Oxaliplatin (OxMdG). Plan E: First-line treatment with OxMdG. The chemotherapy schedules employed in the plans are as follows: MdG: l-folinic acid 175 mg iv infusion over two hours 5-fluorouracil 400 mg/m^2 intravenous bolus over five minutes 5-fluorouracil 2800 mg/m^2 intravenous infusion over 46 hours Cycle repeat: 14 days Irinotecan (single agent): Irinotecan 300-350 mg/m^2 intravenous infusion over 30 minutes Cycle repeat: 21 days IrMdG: Irinotecan 180 mg/m^2 intravenous infusion over 30 minutes l-folinic acid 175 mg/m^2 intravenous infusion over two hours 5-fluorouracil 400 mg/m^2 intravenous bolus over five minutes 5-fluorouracil 2400 mg/m^2 intravenous infusion over 46 hours Cycle repeat: 14 days OxMdG:Oxaliplatin 80 mg/m^2 intravenous infusion over two hours concurrent with l-folinic acid 175 mg intravenous infusion over two hours 5-fluorouracil 400 mg/m^2 intravenous bolus over five minutes 5-fluorouracil 2400 mg/m^2 intravenous infusion over 46 hours Cycle repeat: 14 days In every case, chemotherapy schedules are continued for at least 24 weeks unless disease progression or unacceptable toxicity occurs. Dose reductions or delays for toxicity are defined in the full protocol. |
| Primary outcome measure(s) | Survival from randomisation |
| Secondary outcome measure(s) |
1. Time to failure of first-line treatment
2. Time to failure of protocol treatment plan 3. Objective response rate 4. Patient assessment of quality of life and acceptability of treatment, health economics |
| Sources of funding | Medical Research Council (MRC) (UK) |
| Trial website | |
| Publications |
1. 2005 ASCO Annual Meeting Proceedings abstract in http://meeting.ascopubs.org/cgi/content/abstract/23/16_suppl/3518
2. 2007 results in http://www.ncbi.nlm.nih.gov/pubmed/17630037 3. 2008 results in http://www.ncbi.nlm.nih.gov/pubmed/18509181 4. 2009 results on the association of molecular markers with toxicity outcomes in http://www.ncbi.nlm.nih.gov/pubmed/19858398 5. 2009 results on the effect of KRAS and BRAF mutations on efficacy of treatment agents in http://www.ncbi.nlm.nih.gov/pubmed/19884549 |
| Contact name | Dr Angela Meade |
| Address |
MRC Clinical Trials Unit
222 Euston Road |
| City/town | London |
| Zip/Postcode | NW1 2DA |
| Country | United Kingdom |
| Tel | +44 (0)207 6704700 |
| amm@ctu.mrc.ac.uk | |
| Sponsor | Medical Research Council (MRC) Clinical Trials Unit (UK) |
| Address | 222 Euston Road |
| City/town | London |
| Zip/Postcode | NW1 2DA |
| Country | United Kingdom |
| Tel | +44 (0)207 670 4700 |
| enquiries@ctu.mrc.ac.uk | |
| Sponsor website: | http://www.ctu.mrc.ac.uk/ |
| Date applied | 06/04/2000 |
| Last edited | 28/10/2010 |
| Date ISRCTN assigned | 06/04/2000 |
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| © 2013 ISRCTN unless otherwise stated. | |
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