RATIONALE: SU011248 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Interferon alfa may interfere with the growth of tumor cells and slow the growth of kidney cancer. It is not yet known whether SU011248 is more effective than interferon alfa in treating kidney cancer.

PURPOSE: This randomized phase III trial is studying SU011248 to see how well it works compared to interferon alfa in treating patients with metastatic kidney cancer.

Condition	Treatment or Intervention	Phase
recurrent renal cell cancer renal clear cell carcinoma Stage IV Renal Cell Cancer	Drug: SU011248  Drug: interferon alfa  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy  Procedure: interferon therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase III

Further Study Details: 

OBJECTIVES: Primary

• Compare the time to tumor progression in patients with metastatic renal clear cell carcinoma treated with SU011248 vs interferon alfa as first-line systemic therapy.

Secondary

• Compare the objective response rate in patients treated with these drugs.
• Compare the overall survival of patients treated with these drugs.
• Compare the progression-free survival of patients treated with these drugs.
• Compare patient-reported outcomes, including quality of life, in patients treated with these drugs.
• Determine the safety and tolerability of SU011248 in these patients.
• Compare the cost effectiveness of these drugs in these patients.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to lactate dehydrogenase levels (> 1.5 times upper limit of normal [ULN] vs ≤ 1.5 times ULN), ECOG performance status (0 vs 1), and prior nephrectomy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral SU011248 once daily on days 1-28.
• Arm II: Patients receive interferon alfa subcutaneously on days 1, 3, and 5 weekly for 6 weeks. In both arms, courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, days 1 and 28 of each course, and then at the end of study treatment.

Patients are followed at 30 days and then every 2 months thereafter.

PROJECTED ACCRUAL: A total of 690 patients (345 per treatment arm) will be accrued for this study within 12 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed renal cell carcinoma (RCC)
• Clear cell histology
• Metastatic disease
• Measurable disease
• At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional CT scan or MRI OR ≥ 10 mm by spiral CT scan
• The following are not considered measurable lesions:
• Bone lesions
• Ascites
• Peritoneal carcinomatosis
• Miliary lesions
• Pleural or pericardial effusions
• Lymphangitis of the skin or lung
• Cystic lesions
• Irradiated lesions
• No history of or known brain metastases, spinal cord compression, or carcinomatous meningitis
• No evidence of brain or leptomeningeal disease on CT scan or MRI

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• No concurrent live vaccine for patients receiving interferon-alfa

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (5 times ULN if abnormalities due to underlying malignancy)
• PT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN
• Calcium ≤ 12.0 mg/dL

Cardiovascular

• LVEF ≥ lower limit of normal by MUGA
• No ongoing cardiac dysrhythmias ≥ grade 2
• No atrial fibrillation of any grade
• No prolonged QTc interval (> 450 msec for males or > 470 msec for females)
• None of the following within the within the past 12 months:
• Myocardial infarction
• Severe or unstable angina
• Symptomatic congestive heart failure
• Cerebrovascular accident or transient ischemic attack

Pulmonary

• No pulmonary embolism within the past 12 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 12 weeks after study participation
• No grade 3 hemorrhage occurring less than 4 weeks ago
• HIV negative
• No AIDS-related illness
• No pre-existing abnormal thyroid function that cannot be controlled with medication
• No other severe acute or chronic medical or psychiatric condition that would preclude study participation
• No other laboratory abnormality that would preclude study participation
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior systemic* immunotherapy for RCC
• No concurrent biological response modifiers
• No concurrent immunotherapy
• No concurrent live vaccines for patients receiving interferon alfa

Chemotherapy

• No prior systemic* chemotherapy for RCC
• No concurrent chemotherapy

Endocrine therapy

• No prior systemic* hormonal therapy for RCC
• No concurrent hormonal therapy

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• Prior palliative radiotherapy to metastatic lesion(s) allowed provided there is ≥ 1 measurable lesion not irradiated
• No concurrent radiotherapy

Surgery

• At least 4 weeks since prior major surgery and recovered
• More than 12 months since prior coronary or peripheral artery bypass graft
• No concurrent surgery

Other

• No prior systemic* investigational therapy for RCC
• No concurrent participation on another clinical trial
• No other concurrent anticancer treatment
• No other concurrent investigational drugs NOTE: *Including adjuvant or neoadjuvant therapy

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-5907,  United States; Recruiting

Study chairs or principal investigators

Robert Alan Figlin, MD, FACP,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000398144; UCLA-0406015-01; PFIZER-A6181034; NCT00098657
Record last reviewed:  November 2004
Last Updated:  February 8, 2005
Record first received:  December 7, 2004
ClinicalTrials.gov Identifier:  NCT00098657
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08