Clinical trial NCT00053820: Interferon Alfa With or Without Interleukin-2 and Fluorouracil in Treating Patients With Advanced Metastatic Kidney Cancer
Official title: A Randomized Controlled Trial of Interferon-alpha, Interleukin-2 and 5-Fluorouracil vs. Interferon-alpha Alone in Patients With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Kidney Cancer
Keywords: stage IV renal cell cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
First posted: 2003-02-06
Enrollment: 670
Sex: ALL
Minimum age (years): 18
Maximum age (years): 81
Standard ages: 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 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Survival
Secondary outcomes:
measure: Time to progression as measured by RECIST criteria
measure: Comparison of toxicity levels (Grade III and IV)
measure: Comparison of quality of life before, during, after completion of study treatment
measure: Impact of the treatment regimens on health economics
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Kassel
country: Germany
facility: Klinikum Kassel
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: University Medical Center Rotterdam at Erasmus Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus MC - Sophia Children's Hospital
city: Bratislava
country: Slovakia
facility: National Cancer Institute - Bratislava
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Martin E. Gore, MD
affiliation: Universitair Medisch Centrum St. Radboud - Nijmegen
name: Peter F.A. Mulders, MD, PhD
References:
citation: 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 Feb 20;375(9715):641-8. doi: 10.1016/S0140-6736(09)61921-8. Epub 2010 Feb 10.
citation: Gore ME: Interferon-α (IFN), interleukin-2 (IL2) and 5-fluorouracil (5FU) vs IFN alone in patients with metastatic renal cell carcinoma (mRCC): results of the randomised MRC/EORTC RE04 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-5039, 2008.