Interleukin-12 in Treating Patients With Advanced Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Clinical Trials of IV rhIL-12 With or Without a Test-Dose in Patients With Advanced Malignancies (rhIL-12 NSC# 672423)

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: recombinant interleukin-12


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>See detailed description. | Biological: recombinant interleukin-12<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific