RATIONALE: Interferon alfa may interfere with the growth of tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining interferon alfa with interleukin-2 and fluorouracil may kill more tumor cells. It is not yet known whether interferon alfa is more effective with or without interleukin-2 and fluorouracil in treating metastatic kidney cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa combined with interleukin-2 and fluorouracil to that of interferon alfa alone in treating patients who have advanced metastatic kidney cancer.

Condition	Treatment or Intervention	Phase
Stage IV Renal Cell Cancer	Drug: fluorouracil  Drug: interferon alfa  Drug: interleukin-2  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: cytokine therapy  Procedure: interferon therapy  Procedure: interleukin therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare progression-free and overall survival of patients with advanced metastatic renal carcinoma treated with interferon alfa with or without interleukin-2 and fluorouracil.
• Compare the toxicity of these regimens in these patients.
• Assess the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (Interferon alfa monotherapy): Patients receive interferon alfa subcutaneously (SC) on days 1, 3, and 5. Treatment continues weekly for at least 9 weeks in the absence of disease progression or unacceptable toxicity.
• Arm II (Interferon alfa, interleukin-2, and fluorouracil combination therapy): Patients receive interferon alfa SC on day 1 of weeks 1 and 4 and days 1, 3, and 5 of weeks 2, 3, 5, 6, 7, and 8. Patients also receive interleukin-2 SC twice daily on days 3-5 of weeks 1 and 4 and once daily on days 1, 3, and 5 of weeks 2 and 3. Patients then receive fluorouracil IV on day 1 of weeks 5-8. Treatment repeats every 10 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at 9, 19, and 26 weeks, and then at 8 months.

Patients are followed at 8, 10, and 12 months, every 4 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 670 patients (335 per treatment arm) will be accrued for this study.

Ages Eligible for Study:  18 Years   -   81 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma
• Advanced metastatic disease that requires treatment
• Measurable disease (single bone lesions not included)
• No brain metastasis

PATIENT CHARACTERISTICS: Age

• 18 to 81

Performance status

• WHO 0-1

Life expectancy

• More than 12 weeks

Hematopoietic

• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10 g/dL

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No myocardial infarction within the past 6 months
• No unstable angina pectoris

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• No other concurrent disease or prior malignancy that would preclude study treatments or comparisons
• No concurrent active infection requiring antibiotics

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior biologic therapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• No prior endocrine therapy
• No concurrent corticosteroids

Radiotherapy

• At least 4 weeks since prior radiotherapy

Surgery

• Prior resection of the primary tumor recommended but not required
• No prior major organ allografts

Belgium
      Academisch Ziekenhuis der Vrije Universiteit Brussel, Brussels,  1090,  Belgium; Recruiting
      Institut Jules Bordet, Brussels,  1000,  Belgium; Recruiting
      Onze Lieve Vrouw Ziekenhuis Aalst, Aalst,  B-9300,  Belgium; Recruiting
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium; Recruiting
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium; Recruiting
Germany
      Klinikum Kassel, Kassel,  D-34125,  Germany; Recruiting
Netherlands
      Academisch Ziekenhuis Maastricht, Maastricht,  6202 AZ,  Netherlands; Recruiting
      Erasmus MC - Sophia Children's Hospital, Rotterdam,  3015 GJ,  Netherlands; Recruiting
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands; Recruiting
      Nijmegen Cancer Center at Radboud University Medical Center, Nijmegen,  6500 HB,  Netherlands; Recruiting
      University Medical Center Rotterdam at Erasmus Medical Center, Rotterdam,  3000 CA,  Netherlands; Recruiting
Slovakia
      National Cancer Institute - Bratislava, Bratislava,  833 10,  Slovakia; Recruiting

Study chairs or principal investigators

Martin Eric Gore, MD,  Royal Marsden NHS Trust   
Peter F.A. Mulders, MD, PhD,  Nijmegen Cancer Center at Radboud University Medical Center   

Study ID Numbers:  CDR0000269480; MRC-RE04; EORTC-30012; EU-20231; ISRCTN46518965; NCT00053820
Record last reviewed:  December 2004
Last Updated:  April 5, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00053820
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08