A randomised trial assessing the role of two new agents in the management of advanced colorectal cancer
| ISRCTN | ISRCTN79877428 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN79877428 |
| ClinicalTrials.gov (NCT) | NCT00008060 |
| Protocol serial number | E164/3; CR08 |
| Sponsor | Medical Research Council (MRC) Clinical Trials Unit (UK) |
| Funder | Medical Research Council (MRC) (UK) |
- Submission date
- 06/04/2000
- Registration date
- 06/04/2000
- Last edited
- 15/10/2018
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Angela Meade
Scientific
Scientific
MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom
| Phone | +44 (0)207 6704700 |
|---|---|
| amm@ctu.mrc.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | A randomised trial assessing the role of two new agents in the management of advanced colorectal cancer |
| Study acronym | MRC FOCUS (Fluorouracil, Oxaliplatin, CPT-11, Use and Sequencing) |
| Study objectives | 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. |
| Ethics approval(s) | Added 17/07/2007: Northern and Yorkshire Medical Research Ethics Committee, approval given on 12/11/1999. |
| Health condition(s) or problem(s) studied | Colorectal cancer |
| Intervention | 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. |
| Intervention type | Drug |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Fluorouracil, Oxaliplatin, CPT-11 |
| Primary outcome measure(s) |
Survival from randomisation |
| Key secondary outcome measure(s) |
1. Time to failure of first-line treatment |
| Completion date | 31/12/2003 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | Not Specified |
| Target sample size at registration | 2100 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 12/05/2000 |
| Date of final enrolment | 31/12/2003 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom
NW1 2DA
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 14/07/2007 | Yes | No | |
| Results article | results | 01/06/2008 | Yes | No | |
| Results article | results on the association of molecular markers with toxicity outcomes | 20/11/2009 | Yes | No | |
| Results article | results on the effect of KRAS and BRAF mutations on efficacy of treatment agents | 10/12/2009 | Yes | No | |
| Plain English results | No | Yes |
Editorial Notes
15/10/2018: Cancer Research UK lay results summary link added to Results (plain English).
