Interleukin-12 and Trastuzumab in Treating Patients With Cancer That Has High Levels of HER2/Neu
Study Details
Study Description
Brief Summary
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 such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Phase I trial to study the effectiveness of interleukin-12 and trastuzumab in treating patients who have cancer that has high levels of HER2/neu and has not responded to previous therapy
Detailed Description
OBJECTIVES:
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Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies.
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Determine the safety of this regimen in these patients.
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Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen.
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Characterize natural killer cytokine production in patients treated with this regimen.
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Determine serum interferon gamma levels in patients treated with this regimen.
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 14 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 within 6 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (IL12 and trastuzumab) 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 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease continue treatment for up to 38 additional weeks. |
Biological: recombinant interleukin-12
Given IV
Other Names:
Biological: ABI-007/carboplatin/trastuzumab
Given IV
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) determined according to dose-limiting toxicities (DLTs) graded using Common Terminology Criteria for Adverse Events version 2.0 (CTCAE v2.0) [Up to 52 weeks]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients must have a histologically proven Her2 overexpressing malignancy as determined by any standardized assay currently in clinical use
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Patients must have measurable or evaluable disease
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The patient must have failed standard curative and/or palliative therapies for their disease
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Life expectancy of at least 6 months
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No concurrent malignancy other than non-melanoma skin carcinoma
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Adequate hematopoietic, cardiac, renal, and hepatic function
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Calculated creatinine clearance will be used to assess renal function
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Karnofsky Performance Status index >= 70%
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Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; a woman of childbearing potential is defined as a female who is biologically capable of becoming pregnant
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Normal cardiac ejection fraction by echocardiogram or MUGA (i.e., greater than OSU lower limit of normal)
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Written signed informed consent; the patient must be aware that his/her disease is neoplastic in nature and willingly consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Exclusion Criteria:
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History of significant peripheral neuropathy or significant central nervous system disease
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Brain or central nervous system metastasis at entry
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Active or unstable cardiovascular disease or cardiac disease requiring drug or device intervention; history of coronary artery disease or congestive heart failure
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Pregnant or nursing women
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Surgery, radiotherapy, chemotherapy, or hormonal therapy during the three weeks prior to the initiation of therapy
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Exposure to any investigational drug within three weeks prior to the start of dosing
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Concurrent use of systemic corticosteroids
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Known seropositive for hepatitis B surface antigen
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Known seropositive for HIV antibody
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Serious concurrent infection requiring intravenous antibiotic therapy
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Clinically significant autoimmune disease (e.g., rheumatoid arthritis)
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Clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease
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History of inflammatory bowel disease
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Any other major illness which, in the investigator's judgment, will substantially increase the risk associated with the patient's participation in this study
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Prior therapy with Herceptin
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ohio State University Medical Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: William Carson, Ohio State University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2012-01398
- 99H0185
- U01CA076576
- CDR0000067282