Interleukin-2, Interferon Alfa, and Fluorouracil Compared With Observation in Treating Patients Who Have Undergone Surgery for Kidney Cancer

Adjuvant Interleukin-2, Interferon-alpha and 5-Fluorouracil for Patients With High Risk of Relapse After Surgical Treatment for Renal Cell Carcinoma

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 and interleukin-2 with fluorouracil may kill any remaining tumor cells following surgery. It is not yet known whether combining interferon alfa and interleukin-2 with fluorouracil is more effective than observation after surgery for kidney cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining interleukin-2, interferon alfa, and fluorouracil to that of observation alone in treating patients who have undergone surgery for kidney cancer and are at high risk of relapse.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer
• Intervention / Treatment: Biological: aldesleukin; Biological: recombinant interferon alfa; Drug: fluorouracil; Procedure: adjuvant therapy

Detailed Description

OBJECTIVES:

• Compare the effect of adjuvant combination therapy comprising interleukin-2, interferon alfa, and fluorouracil vs observation only on disease-free survival or overall survival of patients with renal cell carcinoma at high risk of relapse after radical surgery.
• Compare the quality of life of patients treated with these regimens.

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

• Arm I: Patients receive interleukin-2 subcutaneously (SC) on days 3, 4, and 5 of weeks 1 and 4 and on days 1, 3, and 5 of weeks 2 and 3. Patients also receive interferon alfa SC once weekly during weeks 1 and 4 and 3 times weekly during weeks 2, 3, 5, 6, 7, and 8. Patients then receive fluorouracil IV on day 1 of weeks 5, 6, 7, and 8.
• Arm II (control arm): Patients receive no adjuvant treatment before disease progression.

Quality of life is assessed at baseline and at 2 and 6 months after randomization.

Patients are followed monthly for 3 months (arm I only), every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 550 patients (275 per treatment arm) will be accrued for this study within 3 years.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, A-1100
    • Kaiser Franz Josef Hospital
• Belgium
  • Aalst, Belgium, B-9300
    • Onze Lieve Vrouw Ziekenhuis Aalst
  • Ghent, Belgium, B-9000
    • Universitair Ziekenhuis Gent
  • Kortrijk, Belgium, 8500
    • AZ Groeninge - Campus St. Maarten
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
• Hungary
  • Budapest, Hungary, 1125
    • National Institute of Oncology
• Israel
  • Haifa, Israel, 30196
    • Rambam Medical Center
• Italy
  • Varese, Italy, 21100
    • Ospedale Di Circolo E Fondazione Macchi
• Netherlands
  • Amsterdam, Netherlands, 1091 HA
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands, 1105 AZ
    • Akademisch Medisch Centrum
  • Hertogenbosch, Netherlands, 5211 NL
    • Jeroen Bosch ziekenhuis
  • Nijmegen, Netherlands, 6500 HB
    • University Medical Center Nijmegen
  • Rotterdam, Netherlands, 3075 EA
    • Daniel Den Hoed Cancer Center at Erasmus University Medical Center
  • Utrecht, Netherlands, 3584 CX
    • Academisch Ziekenhuis Utrecht
• Turkey
  • Istanbul, Turkey, 81190
    • Marmara University Hospital
  • Izmir, Turkey, 35340
    • Dokuz Eylul University School of Medicine
• United Kingdom
  • Scotland
    • Glasgow, Scotland, United Kingdom, G61 1BD
      • Beatson Institute for Cancer Research - Glasgow

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed primary renal cell carcinoma meeting 1 of the following criteria:

  • Stage T3b, T3c, or T4 tumor
  • Any pT stage and nodal status pN 1 or 2
  • Any pT stage and microscopic positive margins
  • Presence of any microscopic vascular invasion

• Underwent surgical resection of primary tumor within the past month

  • Removal of clinical N+ disease required
• No evidence of metastatic disease
• No evidence of macroscopic residual disease

PATIENT CHARACTERISTICS:

Age

• 75 and under

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 3,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Liver function tests no greater than 1.25 times upper limit of normal (ULN)

Renal

• Creatinine less than 1.5 times ULN

Cardiovascular

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

Other

• Not pregnant or nursing
• No prior or other concurrent malignancies that would preclude study therapy or comparisons
• No other concurrent illness that would preclude study therapy
• No concurrent active infections requiring antibiotic therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent immunotherapy

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• No concurrent corticosteroids
• No concurrent hormonal therapy

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics
• No prior major organ allografts

Other

• No other concurrent investigational drugs, agents, or devices

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Collaborators: University of Glasgow
• Investigators: Study Chair: Pieter H. M. de Mulder, MD, PhD, Universitair Medisch Centrum St. Radboud - Nijmegen; Study Chair: Paul A. Vasey, MD, Beatson Institute for Cancer Research - Glasgow

Publications and helpful links

General Publications

• Aitchison M, Bray CA, Van Poppel H, et al.: Final results from an EORTC (GU Group)/NCRI randomized phase III trial of adjuvant interleukin-2, interferon alpha, and 5-fluorouracil in patients with a high risk of relapse after nephrectomy for renal cell carcinoma (RCC). [Abstract] J Clin Oncol 29 (Suppl 15): A-4505, 2011.

Study record dates

Study Major Dates

• Study Start: February 1, 1998
• Primary Completion (Actual): January 1, 2004

Study Registration Dates

• First Submitted: February 5, 2003
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): September 24, 2012
• Last Update Submitted That Met QC Criteria: September 20, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; stage III renal cell cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Interferons; Interferon-alpha; Aldesleukin; Fluorouracil
• Other Study ID Numbers: EORTC-30955