Clinical trial NCT00053807: Interleukin-2, Interferon Alfa, and Fluorouracil Compared With Observation in Treating Patients Who Have Undergone Surgery for Kidney Cancer
Official title: Adjuvant Interleukin-2, Interferon-alpha and 5-Fluorouracil for Patients With High Risk of Relapse After Surgical Treatment for Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Cancer
Keywords: stage III renal cell cancer
stage IV renal cell cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
Collaborators: name: University of Glasgow
First posted: 2003-02-06
Enrollment: 96
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Kaiser Franz Josef Hospital
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
city: Ghent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus St. Maarten
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Akademisch Medisch Centrum
city: Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus University Medical Center
city: Utrecht
country: Netherlands
facility: Academisch Ziekenhuis Utrecht
city: Istanbul
country: Turkey
facility: Marmara University Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University School of Medicine
city: Glasgow
country: United Kingdom
facility: Beatson Institute for Cancer Research - Glasgow
state: Scotland
Study officials:
affiliation: Universitair Medisch Centrum St. Radboud - Nijmegen
name: Pieter H. M. de Mulder, MD, PhD
role: STUDY_CHAIR
affiliation: University Hospital, Gasthuisberg
name: Hein van Poppel, MD, PhD
role: STUDY_CHAIR
affiliation: Beatson Institute for Cancer Research - Glasgow
name: Paul A. Vasey, MD
role: STUDY_CHAIR
References:
citation: 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.