A Phase I Investigation of IL-12/Pulse IL-2 in Adults With Advanced Solid Tumors

Inclusion Criteria

- INCLUSION CRITERIA:

Adult patients 18 years of age and older.

Pathologically or cytologically-proven diagnosis of non-hematologic malignancy, and the
presence of radiographically or clinically evaluable disease.

Patients with solid tumors including renal, breast, lung carcinomas, as well as sarcomas
for whom a proven more effective therapy does not exist. Patients with renal cell cancer
will 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 variables
in the assessment of the potential hepatic toxicity of this combination.

Negative serologic testing for human immunodeficiency virus (HIV) will be required given
the uncertain impact of rhIL-12 and/or rhIL-2 administration on viral replication, and the
potential alterations in immune responsiveness among patients concurrently infected with
HIV.

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 60
ml/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 prior
to 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 DLCO
greater 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 agents
within 4 weeks prior to study entry.

Patients who have received any of the following agents with known immunomodulatory effects
within 4 weeks prior to study entry: G-CSF/GM-CSF, interferons or interleukins, growth
hormone, IVIG, retinoic acid.

Patients with a history of previous therapy with rhIL-12 will be excluded from study
participation. For patients with renal cell carcinoma, a history of therapy with rhIL-2
will 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 the
principal investigator(s) its use is not necessitated by disease progression. For
patients with disease progression, radiation therapy will be administered as clinically
indicated and the patient will be withdrawn from study participation.