Phase I Trial of rhIL-12 and rHuIFN-a2b in Patients With Metastatic Renal Cell Carcinoma or Malignant Melanoma
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.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Ronald M. Bukowski, MD
The Cleveland Clinic
United States: Food and Drug Administration
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