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

• INCLUSION CRITERIA: Adult patients 18 years of age and older. Pathologically or cytologically-proven diagnosis of non-hematologic malignancy, and thepresence of radiographically or clinically evaluable disease. Patients with solid tumors including renal, breast, lung carcinomas, as well as sarcomasfor whom a proven more effective therapy does not exist. Patients with renal cell cancerwill have received sunitinib or sorefinib or refused this option. Patients must not have received myelosuppressive chemotherapy, hormonal therapy,radiotherapy or immunotherapy within four weeks of entry onto this protocol. Estimated life expectancy of at least 12 weeks. ECOG performance status of 0 or 1. Patients must be free of acute infection or other significant systemic illness. Negative serologic testing for hepatitis B will be required to limit confounding variablesin the assessment of the potential hepatic toxicity of this combination. Negative serologic testing for human immunodeficiency virus (HIV) will be required giventhe uncertain impact of rhIL-12 and/or rhIL-2 administration on viral replication, and thepotential alterations in immune responsiveness among patients concurrently infected withHIV. Adequate hepatic and renal function as evidence by: Transaminases less than 2.5 times the upper limit or normal; Total serum bilirubin less than 2.0 mg/dl; Serum Cr less than 2.0 mg/dl or calculated creatinine clearance of greater than 60ml/min/1.73M(2). Adequate bone marrow function (without growth factor support) as evidence by: Absolute Neutrophil count (ANC) greater than 1500 cells/mm(3); Platelets greater than 100,000/mm(3). For women of childbearing potential, a negative urine pregnancy test within 14 days priorto initiation of study therapy is required. For patients of child-bearing potential,contraceptive precautions must be maintained during study participation. Normal pulmonary function (as documented by PFTs), and for patients over the age of 50,normal stress thallium testing. Normal pulmonary function testing will be defined as DLCOgreater than 60% of predicted and FEVI greater than 70% of predicted.

EXCLUSION CRITERIA: Critically-ill or medically unstable patients. History or a presence of brain metastases. History of coronary artery disease, angina or myocardial infarction. Presence of clinically significant pleural effusion. History of malignant hyperthermia are. Concurrent or history of autoimmune disease. History of congenital or acquired coagulation disorder. Patients with a history of ongoing or intermittent bowel obstruction. Women who are pregnant or lactating will be excluded. Systemic corticosteroids, radiotherapy, chemotherapy, or other investigational agentswithin 4 weeks prior to study entry. Patients who have received any of the following agents with known immunomodulatory effectswithin 4 weeks prior to study entry: G-CSF/GM-CSF, interferons or interleukins, growthhormone, IVIG, retinoic acid. Patients with a history of previous therapy with rhIL-12 will be excluded from studyparticipation. For patients with renal cell carcinoma, a history of therapy with rhIL-2will not exclude patients from study participation. Patients with concurrent administration of any other investigational agent. Patients with hematologic malignancies including leukemia or lymphoma. History of bone marrow or stem-cell transplantation. Intercurrent radiation therapy patients will be allowed on study if in the opinion of theprincipal investigator(s) its use is not necessitated by disease progression. For patientswith disease progression, radiation therapy will be administered as clinically indicatedand the patient will be withdrawn from study participation.