Interleukin-12 in Treating Patients With Advanced Cancer
Phase I Clinical Trials of IV rhIL-12 With or Without a Test-Dose in Patients With Advanced Malignancies (rhIL-12 NSC# 672423)
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
- 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
PATIENT CHARACTERISTICS:
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Arm I
See detailed description.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Michael B. Atkins, MD, Beth Israel Deaconess Medical Center
Publications and helpful links
General Publications
- Gollob JA, Mier JW, Veenstra K, McDermott DF, Clancy D, Clancy M, Atkins MB. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res. 2000 May;6(5):1678-92.
- Gollob JA, Veenstra KG, Mier JW, Atkins MB. Agranulocytosis and hemolytic anemia in patients with renal cell cancer treated with interleukin-12. J Immunother. 2001 Jan-Feb;24(1):91-8. doi: 10.1097/00002371-200101000-00011.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000066286
- BIH-97-1083
- NCI-T97-0053
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