A randomised controlled trial of Interferon-alpha (IFN-alpha), Interleukin-2 (IL-2) and 5 Fluorourcil (5-FU) versus Interferon-alpha alone in patients with advanced renal cell carcinoma

ISRCTN	ISRCTN46518965
DOI	https://doi.org/10.1186/ISRCTN46518965
ClinicalTrials.gov (NCT)	NCT00053820
Protocol serial number	RE04 (E164/5)
Sponsor	Medical Research Council (MRC) (UK)
Funder	Medical Research Council (MRC) (UK)

Submission date: 08/11/2000
Registration date: 08/11/2000
Last edited: 18/10/2018

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

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=61

Contact information

Prof Martin Gore
Scientific

Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	A randomised controlled trial of Interferon-alpha (IFN-alpha), Interleukin-2 (IL-2) and 5 Fluorourcil (5-FU) versus Interferon-alpha alone in patients with advanced renal cell carcinoma
Study objectives	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(s)	Not provided at time of registration.
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Interferon-alpha (IFN-alpha), Interleukin-2 (IL-2) and 5 Fluorourcil (5-FU)
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	31/07/2006

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	1100
Key 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
Key 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
Date of first enrolment	24/04/2001
Date of final enrolment	31/07/2006

Locations

Countries of recruitment

United Kingdom
England
Belgium
Denmark
Germany
Netherlands
Slovakia

Study participating centre

Royal Marsden Hospital

London
SW3 6JJ
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	Peer reviewed?	Patient-facing?
Results article	results	20/02/2010	Yes	No
Other publications	rationale and progress	01/08/2005	Yes	No
Plain English results			No	Yes

Editorial Notes

18/10/2018: Cancer Research UK lay results summary link added to Results (plain English)