Interleukin-12 in Treating Patients With Advanced Cancer

NCT ID: NCT00003330

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-07-31

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

See detailed description.

Group Type: EXPERIMENTAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Interventions

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael B. Atkins, MD

Role: STUDY_CHAIR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

Gollob JA, Mier JW, Veenstra K, McDermott DF, Clancy D, Clancy M, Atkins MB. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res. 2000 May;6(5):1678-92.

Reference Type: RESULT

PMID: 10815886 (View on PubMed)

Gollob JA, Veenstra KG, Mier JW, Atkins MB. Agranulocytosis and hemolytic anemia in patients with renal cell cancer treated with interleukin-12. J Immunother. 2001 Jan-Feb;24(1):91-8. doi: 10.1097/00002371-200101000-00011.

Reference Type: RESULT

PMID: 11211153 (View on PubMed)

Other Identifiers

BIH-97-1083

Identifier Type: -

Identifier Source: secondary_id

NCI-T97-0053

Identifier Type: -

Identifier Source: secondary_id

CDR0000066286

Identifier Type: -

Identifier Source: org_study_id