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 number NCT00008060
Secondary identifying numbers E164/3; CR08
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

MRC Clinical Trials Unit
222 Euston Road
London
NW1 2DA
United Kingdom

Phone +44 (0)207 6704700
Email amm@ctu.mrc.ac.uk

Study information

Study designRandomised controlled trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific titleA randomised trial assessing the role of two new agents in the management of advanced colorectal cancer
Study acronymMRC FOCUS (Fluorouracil, Oxaliplatin, CPT-11, Use and Sequencing)
Study objectives1. 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) studiedColorectal cancer
InterventionThis 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Fluorouracil, Oxaliplatin, CPT-11
Primary outcome measureSurvival from randomisation
Secondary outcome measures1. 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 study start date12/05/2000
Completion date31/12/2003

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexNot Specified
Target number of participants700 in arm one and 350 each in other arms
Key inclusion criteria1. 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 criteria1. 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 enrolment12/05/2000
Date of final enrolment31/12/2003

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centre

MRC Clinical Trials Unit
London
NW1 2DA
United Kingdom

Sponsor information

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

222 Euston Road
London
NW1 2DA
United Kingdom

Phone +44 (0)207 670 4700
Email enquiries@ctu.mrc.ac.uk
Website http://www.ctu.mrc.ac.uk/
ROR logo "ROR" https://ror.org/03x94j517

Funders

Funder type

Research council

Medical Research Council (MRC) (UK)
Government organisation / National government
Alternative name(s)
Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location
United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Plain English results No Yes
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

Editorial Notes

15/10/2018: Cancer Research UK lay results summary link added to Results (plain English).