RATIONALE: Interferon alfa may interfere with the growth of the cancer cells and slow the growth of kidney cancer. Isotretinoin may help kidney cancer cells develop into normal cells. It is not yet known whether interferon alfa plus isotretinoin is more effective than interferon alfa alone for kidney cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without isotretinoin in treating patients who have metastatic kidney cancer.

Condition	Treatment or Intervention	Phase
Stage IV Renal Cell Cancer recurrent renal cell cancer Renal Cell Adenocarcinoma	Drug: interferon alfa  Drug: isotretinoin	Phase III

Further Study Details: 

OBJECTIVES: I. Assess the response rate and response duration of interferon alfa with vs without isotretinoin in patients with bidimensionally measurable progressive metastases from renal cell cancer. II. Assess the toxic effects of these regimens in this patients population. III. Determine the overall survival of this patient population treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive interferon alfa subcutaneously daily. Arm II: Patients receive interferon alfa as in arm I plus oral isotretinoin daily. Treatment continues for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed until death.

PROJECTED ACCRUAL: A total of 296 patients will be accrued for this study.

Ages Eligible for Study:  18 Years   -   75 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed metastatic renal cell adenocarcinoma; Histologic confirmation of metastases desirable; Progression of metastases within 2 months of study; No clinically manifest CNS metastasis
• Bidimensionally measurable metastases, as follows: Lung lesion with diameter greater than 2 cm; Superficial lymph node or skin or subcutaneous lesion with diameter greater than 2.5 cm; Lymph node in the mediastinum or retroperitoneal region, liver lesion, or soft tissue lesion visible on CT or ultrasound with initial diameter greater than 2.5 cm; No bone lesion without surrounding, measurable soft tissue lesion

--Prior/Concurrent Therapy--

• Biologic therapy: No prior immunotherapy
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: No concurrent hormonal therapy
• Radiotherapy: At least 3 months since irradiation of target lesions; Subsequent progression or new lesion required; No concurrent radiotherapy
• Surgery: Prior nephrectomy required; No concurrent surgery
• Other: No concurrent tetracyclines or hepatotoxic drugs

--Patient Characteristics--

• Age: 18 to 75
• Performance status: WHO 0 or 1
• Life expectancy: At least 90 days
• Hematopoietic: WBC greater than 3,000/mm3 OR Absolute granulocyte count greater than 1,500/mm3 OR Platelet count greater than 100,000/mm3
• Hepatic: Bilirubin no greater than 1.1 mg/dL; Lipids no greater than 1.5 times normal
• Renal: Creatinine no greater than 1.6 mg/dL
• Cardiovascular: No congestive heart failure; No significant arrhythmia; No complete bundle branch block
• Pulmonary: No serious concurrent pulmonary illness
• Other: No recent uncontrolled bleeding; No serous effusion; No history of autoimmune disease; No controlled or uncontrolled active infection; No seizure disorder or compromised CNS function; No secondary gastrointestinal dysfunction that could interfere with drug absorption; No psychological condition that would preclude participation or consent; No second malignancy except basal cell skin cancer or carcinoma in situ of the cervix; Not pregnant or nursing; Fertile patients must use effective contraception

Belgium
      Algemeen Ziekenhuis Middelheim, Antwerp,  2020,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      Onze Lieve Vrouw Ziekenhuis Aalst, Aalst,  B-9300,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
      Universitair Ziekenhuis Antwerpen, Edegem,  B-2650,  Belgium
Hungary
      National Institute of Oncology, Budapest,  1125,  Hungary
Italy
      Ospedale di Circolo e Fondazione Macchi, Varese,  21100,  Italy
Netherlands
      Academisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Academisch Ziekenhuis Utrecht, Utrecht,  3508 GA,  Netherlands
      Antoni van Leeuwenhoekhuis, Amsterdam,  1066 CX,  Netherlands
      Groot Ziekengasthuis 's-Hertogenbosch, Hertogenbosch,  5211 NL,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
      Rotterdam Cancer Institute, Rotterdam,  3075 EA,  Netherlands
      University Hospital - Rotterdam Dijkzigt, Rotterdam,  3000 CA,  Netherlands
      University Medical Center Nijmegen, Nijmegen,  NL-6252 HB,  Netherlands
Norway
      Norwegian Radium Hospital, Oslo,  N-0310,  Norway
Russian Federation
      Russian Academy of Medical Sciences Cancer Research Center, Moscow,  115478,  Russian Federation
Switzerland
      Centre Hospitalier Universitaire Vaudois, Lausanne,  CH-1011,  Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland
      Kantonspital Aarau, AARAU,  5001,  Switzerland
      Kantonsspital - Saint Gallen, Saint Gallen,  CH-9007,  Switzerland
      Ospedale San Giovanni, Bellinzona,  CH-6500,  Switzerland
      Ratisches Kantons und Regionalspital, Chur,  CH-7000,  Switzerland
      Universitaetsspital, Zurich,  CH-8091,  Switzerland
Turkey
      Marmara University Hospital, Istanbul,  81190,  Turkey
United Kingdom, England
      Bristol Royal Infirmary, Bristol,  England,  BS2 8HW,  United Kingdom
United Kingdom, Scotland
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom

Study chairs or principal investigators

Nina Aass,  Study Chair,  EORTC Genito-Urinary Tract Cancer Cooperative Group   

Study ID Numbers:  CDR0000064647; EORTC-30951
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002737
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08