RATIONALE: Interleukin-12 may kill tumor cells by stopping blood flow to the tumor and by stimulating a person's white blood cells to kill cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining interleukin-12, chemotherapy, and monoclonal antibody therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of interleukin-12, paclitaxel, and trastuzumab in treating patients who have solid tumors.

Condition	Treatment or Intervention	Phase
recurrent breast cancer recurrent gastric cancer recurrent non-small cell lung cancer recurrent ovarian epithelial cancer Recurrent Small Cell Lung Cancer recurrent endometrial cancer	Drug: interleukin-12  Drug: paclitaxel  Drug: trastuzumab  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: cytokine therapy  Procedure: growth factor antagonist therapy  Procedure: interleukin therapy  Procedure: monoclonal antibody therapy	Phase I

OBJECTIVES:

• Determine the maximum tolerated dose of interleukin-12 when given in combination with paclitaxel and trastuzumab (Herceptin®) in patients with HER2/neu-overexpressing malignancies.
• Determine the response rate and time to progression in patients treated with this regimen.
• Determine the anti-tumor effect of this regimen in these patients.

OUTLINE: This is a dose-escalation study of interleukin-12.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 1 of course 1. Beginning with course 2, patients receive trastuzumab and paclitaxel as in course 1 and interleukin-12 subcutaneously on days 2, 5, 9, 12, 16, and 19. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study within approximately 6 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed HER2/neu-overexpressing (2+ or 3+) malignancy by any standardized assay (fluorescence in-situ hybridization allowed)
• Measurable or evaluable disease
• Failed standard curative therapy
• No brain or CNS metastasis
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Hemoglobin at least 8 g/dL (transfusion or epoetin alfa allowed)
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 3.0 times ULN
• Hepatitis B surface antigen negative

Renal

• Creatinine no greater than 1.5 times ULN
• Calcium no greater than 11 mg/dL (calcium-lowering agents allowed)

Cardiovascular

• No active or unstable cardiovascular disease
• No cardiac disease requiring drug or device intervention
• No coronary artery disease
• No congestive heart failure
• Cardiac ejection fraction normal by echocardiogram or MUGA scan

Neurologic

• No significant peripheral neuropathy
• No significant CNS disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No serious concurrent infection requiring IV antibiotic therapy
• No clinically significant autoimmune disease (e.g., rheumatoid arthritis)
• No clinically significant gastrointestinal bleeding
• No uncontrolled peptic ulcer disease
• No inflammatory bowel disease
• No other major illness that would preclude study participation
• No other concurrent malignancy except non-melanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior interleukin-12
• No prior trastuzumab (Herceptin®)

Chemotherapy

• At least 3 weeks since prior chemotherapy

Endocrine therapy

• At least 3 weeks since prior hormonal therapy
• No concurrent systemic corticosteroids

Radiotherapy

• At least 3 weeks since prior radiotherapy

Surgery

• At least 3 weeks since prior surgery

Other

• At least 3 weeks since prior investigational drug

Ohio
      Arthur G. James Cancer Hospital at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting

Study chairs or principal investigators

William Edgar Carson, MD,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000069102; OSU-99H0326; NCI-84
Record last reviewed:  March 2003
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028535
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-08