OBJECTIVES:

• Determine the toxicity and disease-stabilizing effect of carboxyamidotriazole in patients with metastatic renal cell carcinoma.
• Determine the objective response rate in patients treated with this drug.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to time from diagnosis of metastatic disease to study entry (fewer than 24 months vs 24 months or more).

Patients receive oral carboxyamidotriazole (CAI) daily for 4 weeks. Treatment repeats for 4 courses in the absence of disease progression or unacceptable toxicity.

After 4 courses, patients experiencing complete or partial response continue treatment until disease progression or unacceptable toxicity. Patients with stable disease are randomized to one of two treatment arms.

• Arm I: Patients receive oral CAI as above.
• Arm II: Patients receive a placebo. Treatment repeats every 4 weeks for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression are unblinded and those on placebo begin oral CAI as above.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A maximum of 335 patients will be accrued for this study within 15-25 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma

  • Metastatic or unresectable disease
  • Documented disease progression, even after nephrectomy

• At least 1 unidimensionally measurable lesion

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan

  • The following lesions are not considered measurable:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Abdominal masses not confirmed and followed by imaging
    • Cystic lesions

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• CTC 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 2,000/mm3
• Platelet count at least 75,000/mm3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 2.5 times ULN

Renal:

• Creatinine no greater than 2.0 mg/dL

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No baseline neuropathy or cerebellar dysfunction greater than grade 1

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• No prior carboxyamidotriazole
• No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)
• Concurrent epoetin alfa allowed

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except steroids for adrenal failure or hormones for conditions not related to disease (e.g., insulin for diabetes)

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent palliative radiotherapy

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior surgery