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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma

Conditions
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Kidney Cancer, Melanoma (Skin)

Intervention / Treatment
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* Biological: recombinant interferon alfa
* Biological: recombinant interleukin-12


Participation Criteria
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Eligibility Criteria
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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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Biological: recombinant interferon alfa<br> <br> Biological: recombinant interleukin-12<br> <br> |
| Experimental: Arm II<br>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. | Biological: recombinant interferon alfa<br> <br> Biological: recombinant interleukin-12<br> <br> |
| Experimental: Arm III<br>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. | Biological: recombinant interferon alfa<br> <br> 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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stage IV renal cell cancer, recurrent renal cell cancer, stage IV melanoma, recurrent melanoma