The High-Dose Aldesleukin (IL-2) "Select" Trial for Patients With Metastatic Renal Cell Carcinoma

The High-Dose Aldesleukin (IL-2) "Select" Trial: A Trial Designed to Prospectively Validate Predictive Models of Response to High Dose IL-2 Treatment in Patients With Metastatic Renal Cell Carcinoma

High-dose interleukin 2 (Proleukin, Novartis) (IL-2) is approved by the U.S Food and Drug Administration (FDA) for the treatment of metastatic kidney cancer and is a standard treatment of this disease. At the present time, IL-2 is the only therapy for kidney cancer that can produce a remission of disease that lasts after treatment is completed. However, most patients who receive IL-2 do not benefit and all patients experience potentially dangerous side effects.

Recent research has suggested that certain patients may respond better to IL-2 than others. The Cytokine Working Group is currently conducting a clinical trial that aims to identify and confirm this research and narrow the application of IL-2 to those patients most likely to benefit.

OBJECTIVES:

Primary

• To determine, in a prospective fashion, if the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "good" pathologic predictive features is significantly higher than a historical, unselected patient population.

Secondary

• To determine, in a prospective fashion, the response rate to high-dose IL-2 for patients with metastatic renal cell carcinoma and "poor" pathologic predictive features and to compare this response rate to the response rate of patients with "good" pathologic predictive features.
• To determine if components of other predictive and prognostic models (e.g MSKCI or UCLA criteria) can help to further define the optimal population to receive high-dose IL2 for metastatic renal cell carcinoma.
• To identify features of the baseline immune function (arginine, arginase, T cell zeta chain) of patients with metastatic renal cell carcinoma that are associated with response to high-dose IL-2.
• To identify new proteins or patterns of gene expression that might be associated with high-dose IL-2 responsiveness in order to further narrow the application of IL-2 therapy to those who will benefit the most.

Inclusion Criteria:

• Patients must have histologically confirmed renal cell carcinoma that is metastatic or unresectable.
• If patients have measurable disease restricted to a solitary lesion, its neoplastic nature should be confirmed by cytology/histology.
• Patients must provide access to tissue blocks containing adequate tumor for interpretation and analysis.
• Patients must have measurable disease.
• Patients must have good performance status (ECOG 0 or 1; Karnofsky PS 100-80%).
• Patients must have adequate organ function.
• Patients must have no contraindication of vasopressor agents.
• Patients must be ≥ 18 years of age.

Exclusion Criteria:

• Patients who have received systemic therapy for metastatic disease.
• Patients with organ allografts.
• Patients who require or are likely to require systemic corticosteroid therapy for intercurrent illness.
• Patients with any significant medical disease other than the malignancy (e.g. COPD, patients with ascites or pleural effusions), which in the opinion of the investigator would significantly increase the risk of immunotherapy.
• Patients with a history of another malignancy within the past 5 years other than surgically cured non-melanoma skin cancer, carcinoma-in-situ or Stage I carcinoma of the cervix.