Interleukin-12 and Interferon Alfa in Treating Patients With Metastatic Kidney Cancer or Malignant Melanoma

NCT ID: NCT00004244

Last Updated: 2013-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31
• Study Completion Date: 2008-09-30

Brief Summary

This phase I trial is studying the side effects and best dose of interleukin-12 and interferon alfa in treating patients with metastatic kidney cancer or malignant melanoma. 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. Interferon alfa may interfere with the growth of cancer cells. Combining interleukin-12 and interferon alfa may kill more cancer cells.

Detailed Description

OBJECTIVES:

I. Determine the toxicity of interleukin-12 and interferon alfa in patients with metastatic renal cell carcinoma or malignant melanoma.

II. Determine the maximum tolerated dose of these drugs when concurrently administered in this patient population.

III. Obtain preliminary data on the antitumor efficacy of this combination in these patients.

OUTLINE: This is a dose-escalation study, followed by a randomized study.

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Once the MTD is established, additional patients are accrued and randomized to 1 of the following treatment arms:

ARM I: Patients receive interleukin-12 SC twice a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

ARM II: Patients receive interferon alfa SC three times a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

ARM III: Patients receive treatment with interleukin-12 in combination with interferon alfa at the MTD as described above.

PROJECTED ACCRUAL: A total of 20-30 patients will be accrued for the dose escalation portion of this study. An additional 18 patients (5 in arm I, 5 in arm II, and 8 in arm III) will be accrued to the randomized portion of this study.

Conditions

Kidney Cancer; Melanoma (Skin)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive interleukin-12 SC twice a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

Group Type: EXPERIMENTAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Arm II

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive interferon alfa SC three times a week for 2 weeks, followed by treatment with interleukin-12 in combination with interferon alfa as described above.

Group Type: EXPERIMENTAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Arm III

Patients receive interleukin-12 subcutaneously (SC) twice a week and interferon alfa SC three times a week every week for 4 weeks. Treatment continues in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of interleukin-12 and interferon alfa until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities.

Patients receive treatment with interleukin-12 in combination with interferon alfa at the MTD as described above.

Group Type: EXPERIMENTAL

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Interventions

recombinant interferon alfa

Intervention Type: BIOLOGICAL

recombinant interleukin-12

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma or malignant melanoma
• Strong clinical evidence or biopsy proof of metastases to a site or sites distant from the primary tumor
• Bidimensionally measurable of evaluable disease
• No significant effusions and/or ascites
• No more than 3 prior regimens for metastatic disease
• No known CNS metastases

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.5 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• ALT/AST no greater than 3 times upper limit of normal

Renal:

• Creatinine no greater than 1.8 mg/dL
• Calcium no greater than 11.5 mg/dL

Cardiovascular:

• No history of serious cardiac arrhythmia or cardiac arrhythmia requiring treatment
• No congestive heart failure
• No angina pectoris
• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active peptic ulcer
• No autoimmune disease
• No inflammatory bowel disease
• No local or systemic infections requiring IV antibiotics within the past 28 days
• No known seizure disorder
• No other prior malignancy except basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any curatively treated malignancy in complete remission for at least 3 years
• HIV, hepatitis B surface antigen, and hepatitis C negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Recovered from prior biologic therapy

Chemotherapy:

• Recovered from prior chemotherapy

Endocrine therapy:

• At least 28 days since prior hormonal therapy and recovered
• No concurrent corticosteroids except for replacement steroids

Radiotherapy:

• Recovered from prior radiotherapy
• At least 28 days since prior radiotherapy for control of pain from skeletal lesions

Surgery:

• At least 28 days since prior major surgery requiring general anesthesia
• No organ allografts

Other:

• No concurrent aspirin
• No concurrent barbiturates
• No other concurrent investigational agents

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

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald M. Bukowski, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

CCF-IRB-3063

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0028

Identifier Type: -

Identifier Source: secondary_id

CDR0000067489

Identifier Type: -

Identifier Source: org_study_id