Phase I Clinical Trials of IV rhIL-12 With or Without a Test-Dose in Patients With Advanced Malignancies (rhIL-12 NSC# 672423)
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.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Michael B. Atkins, MD
Beth Israel Deaconess Medical Center
United States: Food and Drug Administration
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