Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Interferon alfa and CCI-779 in Treating Patients With Stage IV or Recurrent Renal Cell Carcinoma (Kidney Cancer)

Basic Trial Information

Objectives

Primary

1. Compare the efficacy of CCI-779 vs interferon alfa vs CCI-779 and interferon alfa, in terms of overall survival, in patients with poor prognosis stage IV or recurrent renal cell carcinoma.

Secondary

1. Compare the response rate (complete and partial response), clinical benefit rate, and progression-free survival of patients treated with these regimens.
2. Compare the duration of overall response, time to treatment failure, and health outcomes in patients treated with this regimen.
3. Compare the safety of these regimens in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed renal cell carcinoma (RCC)
  • Stage IV or recurrent disease

• Poor prognosis, indicated by at least 3 of the following prognostic factors:
  • Less than 1 year from the time of initial RCC diagnosis to study entry
  • Karnofsky performance status of 70
  • Hemoglobin less than lower limit of normal
  • Corrected calcium greater than 10 mg/dL
  • Lactic dehydrogenase greater than 1.5 times upper limit of normal (ULN)

• At least 1 unidimensionally measurable lesion
  • At least 10 mm by spiral CT scan OR at least 20 mm by conventional CT scan

• No CNS metastases
  • Prior CNS metastases allowed provided MRI/CT scan indicates no residual disease

Prior/Concurrent Therapy:

Biologic therapy

• No other concurrent biologic therapy
• No concurrent prophylactic growth factors to support neutrophils
• No concurrent thalidomide

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• No concurrent megestrol or medroxyprogesterone
• No concurrent hormonal therapy
• Concurrent inhaled or replacement corticosteroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery

• More than 4 weeks since prior surgery and recovered
• No concurrent resection of metastases
• No concurrent nephrectomy

Other

• Patients receiving cytochrome P450 3A4 inducers or inhibitors must be on a stable dose for at least 1 week before study randomization
• More than 4 weeks since prior investigational therapy or agents
• No prior systemic anticancer therapy for RCC
• No concurrent laser treatment
• No other concurrent investigational agents
• No concurrent immunosuppressive therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• See Disease Characteristics
• Karnofsky 70-100%

Life expectancy

• At least 8 weeks

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 8.0 g/dL

Hepatic

• See Disease Characteristics
• Bilirubin no greater than 1.5 times ULN
• AST no greater than 3 times ULN (5 times ULN if liver metastases are present)
• Hepatitis B negative
• Hepatitis C negative

Renal

• See Disease Characteristics
• Creatinine no greater than 1.5 times ULN

Cardiovascular

• No myocardial infarction within the past 6 months
• No unstable angina
• No life-threatening arrhythmias requiring ongoing maintenance therapy

Pulmonary

• No known pulmonary hypertension
• No pneumonitis

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study treatment
• HIV negative
• Fasting cholesterol no greater than 350 mg/dL
• Triglycerides no greater than 400 mg/dL
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No active infection
• No other major illness that would increase the risk associated with study participation
• No known hypersensitivity to any of the components in CCI-779 or interferon alfa
• No other medical reason that would preclude adequate premedication (e.g., antihistamine or anti-inflammatory agents) before the administration of study drugs
• No immunocompromised status
• No other concurrent serious illness

Expected Enrollment

A total of 620 patients (206 per treatment arm) will be accrued for this study within 20 months.

Outline

This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 3 treatment arms.

• Arm I: Patients receive interferon alfa subcutaneously 3 times weekly.

• Arm II: Patients receive CCI-779 IV over 30 minutes once weekly.

• Arm III: Patients receive interferon alfa as in arm I on week 1 only. Beginning on week 2 and for all subsequent weeks, patients receive interferon alfa as in arm I and CCI-779 as in arm II.

Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 2 months for survival.

Figlin RA, de Souza P, McDermott D, et al.: Analysis of PTEN and HIF-1alpha and correlation with efficacy in patients with advanced renal cell carcinoma treated with temsirolimus versus interferon-alpha. Cancer 115 (16): 3651-60, 2009.[PUBMED Abstract]

Hudes G, Carducci M, Tomczak P, et al.: Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356 (22): 2271-81, 2007.[PUBMED Abstract]

Hudes G, Carducci M, Tomczak P, et al.: A phase 3, randomized, 3-arm study of temsirolimus (TEMSR) or interferon-alpha (IFN) or the combination of TEMSR + IFN in the treatment of first-line, poor-risk patients with advanced renal cell carcinoma (adv RCC). [Abstract] J Clin Oncol 24 (Suppl 18): A-LBA4, 2006.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Robert Figlin, MD, FACP, Principal investigator (Contact information may not be current)		Ph: 310-825-5268; 888-798-0719

Registry Information
Official Title		A Phase III, Three-Arm, Randomized, Open-Label Study Of Interferon Alfa Alone, CCI-779 Alone, And The Combination Of Interferon Alfa And CCI-779 In First-Line Poor-Prognosis Subjects With Advanced Renal Cell Carcinoma
Trial Start Date		2003-08-06
Registered in ClinicalTrials.gov		NCT00065468
Date Submitted to PDQ		2003-08-28
Information Last Verified		2005-03-24
NCI Grant/Contract Number		CA16042

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