Condition category
Cancer
Date applied
08/11/2000
Date assigned
08/11/2000
Last edited
14/07/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof Martin Gore

ORCID ID

Contact details

Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00053820

Protocol/serial number

RE04 (E164/5)

Study information

Scientific title

Acronym

Study hypothesis

1. The value of triple combination therapy in terms of overall survival in patients with advanced metastatic renal cell carcinoma compared with IFN-alpha alone
2. The value of triple combination therapy in terms of progression-free survival time and toxicity compared with IFN-alpha alone
3. The Quality of Life of patients in both treatment arms during therapy and
follow-up
4. The health economic implications of using triple therapy compared to the control regimen

Ethics approval

Not provided at time of registration.

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Renal Cancer

Intervention

Arm 1: IFN-alpha until progression
Arm 2: IFN-alpha, IL-2 and 5-FU (max 2 cycles)

Intervention type

Drug

Phase

Not Specified

Drug names

Interferon-alpha (IFN-alpha), Interleukin-2 (IL-2) and 5 Fluorourcil (5-FU)

Primary outcome measures

The primary endpoint is survival. The primary endpoint, which will be used to evaluate the efficacy of the treatment regimens, will be time to death. All deaths should be reported immediately and time to death will be calculated from the date of randomisation.

Secondary outcome measures

1. Time to disease progression. Progression is defined according to the RECIST guidelines
2. Comparison of toxicity levels, principally grade III/IV
3. Quality of life will be assessed before, during and after treatment
4. The impact of the treatment regimens on health economics will also be evaluated

Overall trial start date

24/04/2001

Overall trial end date

31/07/2006

Reason abandoned

Eligibility

Participant inclusion criteria

1. Histologically proven renal cell carcinoma. Material may be obtained from the primary tumour or the metastases
2. Advanced metastatic disease – that, in the opinion of the investigator, requires treatment. (We would recommend that patients have undergone resection of their primary tumour prior to entry into the trial but this is not mandatory)
3. At least one measurable lesion. Measurements must be taken within the 4 week period before the start of treatment (single bone lesions should not be included due to assessing response)
4. WHO performance status 0 or 1
5. Normal haematological parameters (WBC >3 x 109/l; platelets >100 x 109/l; haemoglobin >10g/dl). This assessment should be carried out within 7 days before randomisation
6. Creatinine levels must be within normal limits for institution. If creatinine raised, then EDTA or creatinine clearance should be greater than 60ml/min
7. Life expectancy greater than 12 weeks
8. Written informed consent
9. Male or female patient of any ethnic group more than 18 years in age

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1100

Participant exclusion criteria

1. No radiotherapy to target lesions during trial therapy
2. Previous chemotherapy, endocrine therapy or treatment with biological agents
3. No current or previous brain metastasis
4. Unstable angina pectoris or recent (6 month) myocardial infarction
5. Evidence of active infections requiring antibiotic therapy
6. Patients with major organ allografts (IL-2 may increase T-cell mediated rejection and immunosuppressive agents are likely to reduce efficacy of IL-2 and IFN-alpha
7. Patients who require or are likely to require corticosteroids for intercurrent disease
8. Pregnant or lactating women
9. Other disease or previous malignancy likely to interfere with the protocol treatments or comparisons
10. Patients with concurrent malignancy, unless they have remained free of the disease attributed to the malignancy for more than 5 years

Recruitment start date

24/04/2001

Recruitment end date

31/07/2006

Locations

Countries of recruitment

Belgium, Denmark, Germany, Netherlands, Slovakia, United Kingdom

Trial participating centre

Royal Marsden Hospital
London
SW3 6JJ
United Kingdom

Sponsor information

Organisation

Medical Research Council (MRC) (UK)

Sponsor details

20 Park Crescent
London
W1B 1AL
United Kingdom
+44 20 7636 5422
clinical.trial@headoffice.mrc.ac.uk

Sponsor type

Research council

Website

http://www.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

2005 rationale and progress in: http://www.ncbi.nlm.nih.gov/pubmed/16097560
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20153039

Publication citations

  1. Results

    Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF, Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial., Lancet, 2010, 375, 9715, 641-648, doi: 10.1016/S0140-6736(09)61921-8.

  2. Larkin JM, Gore ME, The MRC randomised-controlled trial of interferon-alpha, interleukin-2 and 5-fluorouracil vs interferon-alpha alone in patients with advanced renal cell carcinoma (RE04): rationale and progress., Clin Oncol (R Coll Radiol), 2005, 17, 5, 319-321.

Additional files

Editorial Notes