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
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
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.
- 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
- 18 and over
- ECOG 0-1
- At least 3 months
- WBC at least 3,000/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin at least 9.5 g/dL
- Bilirubin no greater than 1.5 mg/dL
- ALT/AST no greater than 3 times upper limit of normal
- Creatinine no greater than 1.8 mg/dL
- Calcium no greater than 11.5 mg/dL
- 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
- 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:
- Recovered from prior biologic therapy
- Recovered from prior chemotherapy
- At least 28 days since prior hormonal therapy and recovered
- No concurrent corticosteroids except for replacement steroids
- Recovered from prior radiotherapy
- At least 28 days since prior radiotherapy for control of pain from skeletal lesions
- At least 28 days since prior major surgery requiring general anesthesia
- No organ allografts
- No concurrent aspirin
- No concurrent barbiturates
- No other concurrent investigational agents