Phase I trial to study the effectiveness of interleukin-12 in treating patients who have
advanced cancer. 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.
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.
- Histologically confirmed malignancy that is metastatic or unresectable and for which
standard curative or palliative measures do not exist or are no longer effective
- Advanced measurable or evaluable disease that is clearly progressive
- No brain metastases
- Age: 18 and over
- Performance status: ECOG 0-1 Karnofsky 80-100%
- Life expectancy: At least 3 months
- WBC greater than 4,000/mm3
- Platelet count greater than 100,000/mm3
- Bilirubin less than 1.5 mg/dL
- SGOT/SGPT less than 2 times normal
- Creatinine less than 1.5 mg/dL
- Creatinine clearance at least 60 mL/min
- No congestive heart failure
- No coronary artery disease
- No serious cardiac arrhythmias
- No evidence of prior myocardial infarction on EKG
- Not pregnant or nursing
- Fertile patients must use effective contraception
- Not HIV positive
- No seizure disorders
- No active infection that requires antibiotic therapy
- No significant medical disease other than the malignancy
PRIOR CONCURRENT THERAPY:
- No more than 2 prior biological response modifier treatment regimen
- No immunotherapy within the past 4 weeks
- No prior interleukin-12
- No more than 2 prior chemotherapy regimens
- At least 4 weeks since chemotherapy and recovered
- At least 6 weeks since nitrosoureas or mitomycin and recovered
- No concurrent chemotherapy
- At least 4 weeks since hormone therapy and recovered
- No concurrent hormone therapy
- No concurrent corticosteroids
- At least 4 weeks since radiotherapy and recovered
- No concurrent radiotherapy
- No organ allografts
- At least 2 weeks since intravenous antibiotics