Condition category
Cancer
Date applied
06/04/2000
Date assigned
06/04/2000
Last edited
28/10/2010
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Angela Meade

ORCID ID

Contact details

MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom
+44 (0)207 6704700
amm@ctu.mrc.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00008060

Protocol/serial number

E164/3; CR08

Study information

Scientific title

Acronym

MRC FOCUS (Fluorouracil, Oxaliplatin, CPT-11, Use and Sequencing)

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.

Ethics approval

Added 17/07/2007: Northern and Yorkshire Medical Research Ethics Committee, approval given on 12/11/1999.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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 names

Fluorouracil, Oxaliplatin, CPT-11

Primary outcome measures

Survival from randomisation

Secondary outcome measures

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

Overall trial start date

12/05/2000

Overall trial end date

31/12/2003

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Not Specified

Gender

Not Specified

Target number of participants

700 in arm one and 350 each in other arms

Participant 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

Recruitment start date

12/05/2000

Recruitment end date

31/12/2003

Locations

Countries of recruitment

United Kingdom

Trial participating centre

MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom

Sponsor information

Organisation

Medical Research Council (MRC) Clinical Trials Unit (UK)

Sponsor details

222 Euston Road
London
NW1 2DA
United Kingdom
+44 (0)207 670 4700
enquiries@ctu.mrc.ac.uk

Sponsor type

Research council

Website

http://www.ctu.mrc.ac.uk/

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

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

Publication citations

  1. Results

    Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, Smith DB, Shepherd S, Maraveyas A, Ferry DR, Meade AM, Thompson L, Griffiths GO, Parmar MK, Stephens RJ, , , Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial., Lancet, 2007, 370, 9582, 143-152, doi: 10.1016/S0140-6736(07)61087-3.

  2. Results

    Braun MS, Richman SD, Quirke P, Daly C, Adlard JW, Elliott F, Barrett JH, Selby P, Meade AM, Stephens RJ, Parmar MK, Seymour MT, Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial., J. Clin. Oncol., 2008, 26, 16, 2690-2698, doi: 10.1200/JCO.2007.15.5580.

  3. Results on the association of molecular markers with toxicity outcomes

    Braun MS, Richman SD, Thompson L, Daly CL, Meade AM, Adlard JW, Allan JM, Parmar MK, Quirke P, Seymour MT, Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial., J. Clin. Oncol., 2009, 27, 33, 5519-5528, doi: 10.1200/JCO.2008.21.6283.

  4. Results on the effect of KRAS and BRAF mutations on efficacy of treatment agents

    Richman SD, Seymour MT, Chambers P, Elliott F, Daly CL, Meade AM, Taylor G, Barrett JH, Quirke P, KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial., J. Clin. Oncol., 2009, 27, 35, 5931-5937, doi: 10.1200/JCO.2009.22.4295.

Additional files

Editorial Notes