Interleukin-12 in Treating Patients With Advanced Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Biological: recombinant interleukin-12

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003330

NCI-T97-0053

CDR0000066286

BIH-97-1083

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

Arm I

Experimental group

Description:

See detailed description.

Treatment:

Biological: recombinant interleukin-12