Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of the HER2/neu Protein

This study is currently recruiting patients.

Sponsored by

National Cancer Institute (NCI)

Arthur G. James Cancer Hospital

Purpose

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. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of the HER2/neu protein and has not responded to previous therapy.

Study Type: Treatment

Official Title: Phase I Study of Interleukin-12 and Trastuzumab (Herceptin) in Patients with HER2-Neu Overexpressing Malignancies

Further Study Details: OBJECTIVES: I. Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies. II. Evaluate the safety and dose limiting toxicity of this regimen in these patients. III. Define a recommended starting dose of IL-12 for a Phase II study. IV. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen. V. Characterize natural killer cytokine production in these patients in response to this regimen. VI. Determine serum interferon gamma levels in these patients in response to this regimen.  PROTOCOL OUTLINE: This is a dose escalation study of interleukin-12 (IL-12). Patients receive an initial loading dose of trastuzumab IV over 90 minutes on day 1 of the first week and a maintenance dose of trastuzumab IV over 30-90 minutes on day 1 of each subsequent week. Patients receive IL-12 IV on days 2 and 5 beginning on week 3. Treatment with maintenance trastuzumab and IL-12 repeats weekly for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks. Cohorts of 3-6 patients receive escalating doses of IL-12 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity. Patients are followed every 3 months for 1 year and then every 6 months thereafter for survival.  PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study over 6 months.  

Eligibility

Ages Eligible for Study:  18 Years  and above Criteria

PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Histologically proven malignancy with overexpression of HER2-Neu Must have failed standard curative and/or palliative therapies Measurable or evaluable disease No concurrent brain or CNS metastases No significant prior CNS disease --Prior/Concurrent Therapy-- Biologic therapy: No prior trastuzumab 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 agents --Patient Characteristics-- Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: At least 6 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Hemoglobin at least 9 g/dL (epoetin alfa or prior transfusion allowed) Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN) SGOT and SGPT no greater than 3 times ULN Renal: Creatinine no greater than 1.5 times ULN Creatinine clearance at least 60 mL/min Calcium no greater than 11 mg/dL (calcium lowering agents allowed) Cardiovascular: Normal cardiac ejection fraction by echocardiogram or MUGA No active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention No prior coronary artery disease No prior congestive heart failure Gastrointestinal: No clinically significant gastrointestinal bleeding No uncontrolled peptic ulcer disease No prior inflammatory bowel disease Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception before and during study HIV negative Hepatitis B surface antigen negative No other concurrent malignancy except nonmelanomatous skin cancer No significant prior peripheral neuropathy No serious concurrent infection requiring IV antibiotic therapy No clinically significant autoimmune disease (e.g., rheumatoid arthritis) No other major illness that would increase risk of participation in study

Location and Contact Information

Ohio

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

Charles L. Shapiro       614-293-7530   

Study chairs or principal investigators

William Edgar Carson, III,  Study Chair

Arthur G. James Cancer Hospital    

More Information

Study ID Numbers  199/14475;   OSU-99H0185; NCI-T99-0032

NLM Identifier  NCT00004074

Date study started July 28, 1999

Last Updated  December 1, 1999

Back