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| Sponsors and Collaborators: |
Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI) |
|---|---|
| Information provided by: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT00004074 |
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 such as trastuzumab 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 HER2/neu and has not responded to previous therapy.
| Condition | Intervention | Phase |
|---|---|---|
|
Cancer |
Biological: recombinant interleukin-12 Biological: trastuzumab |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment |
| Official Title: | A Phase I Trial of Herceptin and Interleukin-12 |
| Estimated Enrollment: | 15 |
| Study Start Date: | July 1999 |
| Primary Completion Date: | February 2009 (Final data collection date for primary outcome measure) |
OBJECTIVES: I. Determine the maximum tolerated dose of interleukin-12 (IL-12) when combined with trastuzumab in patients with HER2-Neu overexpressing malignancies. II. Determine the safety of this regimen in these patients. III. Analyze any expression of interferon-inducible genes in tumor tissues of these patients after receiving this regimen. IV. Characterize natural killer cytokine production in patients treated with this regimen. V. 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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically proven malignancy with overexpression of HER2-Neu (1-3+) Must have failed standard curative and/or palliative therapies Measurable or evaluable disease No concurrent brain or CNS metastases No significant prior CNS disease
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 Hepatitis B surface antigen negative 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: Cardiac ejection fraction normal 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 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
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
Contacts and Locations| United States, Ohio | |
| Arthur G. James Cancer Hospital - Ohio State University | |
| Columbus, Ohio, United States, 43210-1240 | |
| Study Chair: | William E. Carson, MD | Arthur G. James Cancer Hospital & Richard J. Solove Research Institute |
More Information
| Study ID Numbers: | CDR0000067282, OSU-99H0185, NCI-T99-0032 |
| Study First Received: | December 10, 1999 |
| Last Updated: | March 5, 2009 |
| ClinicalTrials.gov Identifier: | NCT00004074 History of Changes |
| Health Authority: | United States: Federal Government |
|
stage III colon cancer stage IV colon cancer stage IV breast cancer stage IIIA breast cancer recurrent breast cancer stage III gastric cancer stage IV gastric cancer recurrent gastric cancer occult non-small cell lung cancer stage IIIB breast cancer recurrent non-small cell lung cancer stage III pancreatic cancer recurrent pancreatic cancer stage III rectal cancer stage IV rectal cancer |
recurrent colon cancer recurrent rectal cancer stage IV anal cancer recurrent anal cancer stage III esophageal cancer stage IV esophageal cancer stage IIIA anal cancer stage IIIB anal cancer recurrent esophageal cancer stage III cervical cancer recurrent cervical cancer stage IVB cervical cancer stage IVA cervical cancer inflammatory breast cancer stage III renal cell cancer |
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Rectal Neoplasms Thyroid Cancer, Papillary Pancreatic Neoplasms Pancreatic Polypeptide Thyroid Cancer, Medullary Vaginal Cancer Breast Cancer, Male Anal Cancer Squamous Cell Carcinoma Carcinoma, Adenoid Cystic Thyroid Cancer, Follicular Lung Neoplasms Zollinger-Ellison Syndrome Trastuzumab Neoplasm Metastasis |
Salivary Gland Diseases Vaginal Neoplasms Nasopharyngeal Carcinoma Testicular Cancer Carcinoma, Islet Cell Adjuvants, Immunologic Urinary Bladder Neoplasms Insulinoma Breast Neoplasms Esophageal Cancer Testicular Neoplasms Carcinoma Gastrinoma Breast Neoplasms, Male Esophageal Disorder |
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Interleukin-12 Immunologic Factors Antineoplastic Agents Therapeutic Uses Growth Substances Physiological Effects of Drugs |
Adjuvants, Immunologic Trastuzumab Growth Inhibitors Angiogenesis Modulating Agents Angiogenesis Inhibitors Pharmacologic Actions |
