Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific
Brief summary
Phase I trial to study the effectiveness of interleukin-12 in treating patients who have advanced cancer. 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.
Detailed description
OBJECTIVES: I. Determine the toxicity profile and maximum tolerated dose (MTD) of intravenous interleukin-12 (IL-12) administered biweekly for 6-18 weeks in the presence and absence of a test dose in patients with metastatic or unresectable malignancies. II. Determine the optimal timing for administration of an IL-12 test dose, based on its impact on secondary biologic parameters in these patients. III. Determine the antitumor effects of IL-12 administered according to this schedule, with and without a test dose, in these patients. IV. Determine the effect of a test dose on toxicity profile, MTD, tumor response and various biologic phenomena in serum, and, where possible, tumor and liver in these patients. OUTLINE: This is a 3-part dose escalation study. In Part A, patients receive intravenous interleukin-12 (IL-12) twice a week for 6 weeks. Courses are repeated until patients achieve a complete response or there is disease progression. Dose escalation of IL-12 continues in cohorts of 3-6 patients until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose below that at which 2 of 6 patients experience dose limiting toxicity (DLT). In Part B, patients receive a single test dose of IL-12 administered intravenously at a 1, 2, or 3 week interval prior to starting the multidose twice a week regimen as in Part A. Cohorts of 4 patients will receive IL-12 at the MTD obtained in Part A. In Part C, patients receive IL-12 at one dose level above the MTD obtained in Part A using the optimal schedule for the test dose determined in Part B. Dose escalation continues in cohorts of 3-6 patients until the MTD is determined. The MTD is defined as the dose below that at which 2 of 6 patients experience DLT. Patients may continue to receive IL-12 until they have no measurable disease or until disease progression.
Interventions
BIOLOGICALrecombinant interleukin-12
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * Advanced measurable or evaluable disease that is clearly progressive * No brain metastases PATIENT CHARACTERISTICS: * Age: 18 and over * Performance status: ECOG 0-1 Karnofsky 80-100% * Life expectancy: At least 3 months * WBC greater than 4,000/mm3 * Platelet count greater than 100,000/mm3 * Bilirubin less than 1.5 mg/dL * SGOT/SGPT less than 2 times normal * Creatinine less than 1.5 mg/dL * Creatinine clearance at least 60 mL/min * No congestive heart failure * No coronary artery disease * No serious cardiac arrhythmias * No evidence of prior myocardial infarction on EKG * Not pregnant or nursing * Fertile patients must use effective contraception * Not HIV positive * No seizure disorders * No active infection that requires antibiotic therapy * No significant medical disease other than the malignancy PRIOR CONCURRENT THERAPY: * No more than 2 prior biological response modifier treatment regimen * No immunotherapy within the past 4 weeks * No prior interleukin-12 * No more than 2 prior chemotherapy regimens * At least 4 weeks since chemotherapy and recovered * At least 6 weeks since nitrosoureas or mitomycin and recovered * No concurrent chemotherapy * At least 4 weeks since hormone therapy and recovered * No concurrent hormone therapy * No concurrent corticosteroids * At least 4 weeks since radiotherapy and recovered * No concurrent radiotherapy * No organ allografts * At least 2 weeks since intravenous antibiotics
Countries
United States
Outcome results
None listed