Medroxyprogesterone or Interferon and/or Aldesleukin in Treating Patients With Metastatic Kidney Cancer

OBJECTIVES:

Primary

• Determine the overall survival of patients with metastatic renal cell adenocarcinoma treated with medroxyprogesterone vs recombinant interferon alfa-2a and/or aldesleukin.

Secondary

• Determine the objective response rate (complete and partial) of patients treated with these regimens.
• Determine the progression-free survival of patients treated with these regimens.
• Determine the toxicity of these regimens in these patients.
• Evaluate the quality of life of patients before and after induction treatment with these regimens (week 10).

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I (medroxyprogesterone): Patients receive oral medroxyprogesterone once daily for 12 weeks. Patients may receive a second 12-week course in the presence of responding or stable disease. Quality of life is assessed at baseline and at weeks 12 and 24.
• Arm II (recombinant interferon alfa-2a): Patients receive recombinant interferon alfa-2a subcutaneously (SC) 3 times weekly for 12 weeks. Patients may receive a second 12-week course in the presence of responding or stable disease. Quality of life is assessed as in arm I.
• Arm III (aldesleukin): Patients receive aldesleukin SC twice daily on days 1-5, 8, 9, 15, 16, 22, and 23 and once daily on days 10-12, 17-19, and 24-26. Courses repeat beginning in weeks 6, 13, and 20. Quality of life is assessed at baseline and at weeks 10 and 24.
• Arm IV (recombinant interferon alfa-2a and aldesleukin): Patients receive recombinant interferon alfa-2a as in arm II and receive aldesleukin as in arm III. Quality of life is assessed as in arm III.

After completion of study treatment, patients are followed periodically for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 456 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic renal cell adenocarcinoma, meeting 1 of the following criteria:

• More than 1 metastatic site and good performance status (Karnofsky score 80-100%)
• Sole metastatic site with Karnofsky score = 80%

• Karnofsky 90% or 100% not eligible
• No combination of several metastatic sites and liver metastases and a time interval from primary tumor to metastases of < 1 year
• Nonmeasurable disease and/or few numbers of lesions must be confirmed histologically and as progressive disease
• The following metastases are allowed:

• Lung with or without mediastinum lymph nodes
• Bone
• Pleura (solid or liquid with positive cytology)
• Thoracic lymph nodes
• Abdominal lymph nodes
• Superficial lymph nodes
• Liver
• Subcutaneous skin/tissue
• Contralateral kidney
• Nephrectomy site
• Other organs
• Prior metastases allowed provided the following criteria are met:

• Evidence of progressive disease within the past 3 months
• Metastases evaluated by noninvasive methods
• No evidence of active brain metastases

• Prior brain metastases allowed provided all of the following criteria are met:

• Disease is stable
• Reductive therapy (surgery or radiotherapy) completed at least 3 weeks prior to study entry
• Metastases have not progressed (confirmed by CT scan or MRI)
• No concurrent corticosteroids required

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• Creatinine < 1.8 mg/dL
• Hematocrit ≥ 30%
• WBC ≥ 4,000/mm^3
• Platelet count ≥ 120,000/mm^3
• Bilirubin normal
• LVEF ≥ 50%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No HIV positivity
• No severe infection requiring antibiotic therapy
• No chronic hepatitis
• No severe lung, liver or kidney condition that would preclude study treatment
• No hepatitis B surface antigen positivity
• No severe neuropsychiatric condition or epilepsy
• No serious thromboembolitic disorder
• No severe cardiac dysfunction (e.g., congestive heart failure, uncontrolled hypertension, serious arrhythmia, or coronary disease)
• No other prior or concurrent primary malignancies except for basal cell skin cancer or carcinoma in situ of the cervix
• No geographical, psychological, or familial condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• More than 6 weeks since prior wide-field radiotherapy
• No prior systemic chemotherapy
• No prior organ transplantation
• No prior cytokines
• No concurrent hormonal therapy
• No concurrent anticancer chemotherapy
• No concurrent corticosteroids
• No other concurrent immunotherapy
• No other concurrent investigational agents or therapies