Combination Therapy of Interleukin-12 and Interleukin-2 to Treat Advanced Cancer

Background: Renal cell cancer responds to treatment with a variety of antiangiogenic and immunomodulatory drugs. In the RENCA model of renal cell cancer the combination of IL-12 and pulse IL-2 cures 88-100% of mice with established tumors. The tumor regression observed in this model is due to both antiangiogenic and immunologic effects. Objective: To define the maximum tolerated dose and dose-limiting toxicities of recombinant human IL-12 administered intravenously in combination with intermittent pulse recombinant human IL-2 in adults with various advanced and/or refractory solid tumors. To evaluate the pharmacokinetics of intravenous rhIL-12/pulse rhIL-2 administration in adults with various advanced and/or refractory solid tumors. To provide a preliminary assessment of the ability of rhIL-12/pulse rhIL-2 to modify neovascularization and gene expression in the local tumor site, and to induce a measurable antitumor effect in adults with various advanced and/or refractory solid tumors. To evaluate the immunomodulatory activity of combined systemic administration of rhIL-12/pulse rhIL-2. Eligibility: Patients with advanced solid tumors for whom a proven more effective therapy does not exist. Patients with renal cell cancer will be required to have received sunitinib or sorefinib or refused this option. The patient must have normal organ function and a life expectancy of at least 12 Weeks. Normal pulmonary function (as documented by PFTs), and for patients over the age of 50, normal stress thallium testing. No prior treatment with IL-12. Design: Phase I dose escalation with an expansion cohort of 10 patients treated at the maximum tolerated dose. Patients will be hospitalized for treatment. IL-2 will be given intravenously every 8 hours on day 1 and this will be followed by intravenous administration of IL-12 every other day for three doses on days 2, 4, and 6. After two days of rest the schedule will be repeated. Cycles will be repeated every 36 days. Tumor response will be evaluated after every treatment. Stable or responding patients will continue treatment with evaluations after every cycle of treatment.