RATIONALE: Interleukin-12 may stimulate a person's white blood cells to kill cancer cells. Interferon alfa may interfere with the growth of the cancer cells. Combining interleukin-12 with interferon alfa may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining interleukin-12 and interferon alfa in treating patients who have residual, recurrent, or metastatic malignant melanoma or other advanced cancer that has not responded to standard therapy.

Condition	Treatment or Intervention	Phase
Cancer	Drug: interferon alfa  Drug: interleukin-12	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of interferon alfa when preceded by a single dose of interleukin-12 in patients with recurrent or metastatic melanoma or other advanced malignancies.

PROTOCOL OUTLINE: This is a dose escalation study.

Cohorts of 3 patients receive interleukin-12 IV push on day 1, followed by escalating doses of interferon alfa by subcutaneous injection at 24, 48, 72, 96 and 120 hours. Courses repeat every 2 weeks for 6 months (12 courses total) in the absence of unacceptable toxicity and disease progression. Patients achieving partial response or stable disease at the completion of 6 months of therapy may receive additional courses of therapy for up to 24 months.

Dose escalation of interferon alfa continues in subsequent cohorts in the absence of dose limiting toxicity (DLT). If 1 of 3 patients experiences DLT at a dose level, then 3 additional patients are entered at that dose level. If 2 of 6 patients experience DLT, then dose escalation stops. The maximum tolerated dose is defined as 1 level below that dose at which 2 or more of 6 patients experience DLT.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: Approximately 30-40 patients will be accrued into this study.

Ages Eligible for Study:  13 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed residual, recurrent, or metastatic malignant melanoma or other advanced malignancies
• Must have failed standard curative and/or palliative therapies
• No brain or central nervous system metastases

--Prior/Concurrent Therapy--

• Biologic therapy: At least 4 weeks since prior biologic therapy
• Chemotherapy: At least 4 weeks since prior chemotherapy
• Endocrine therapy: No concurrent systemic corticosteroids
• Radiotherapy: At least 2 weeks since prior local radiotherapy
• Surgery: At least 2 weeks since surgery
• Other: At least 4 weeks since prior investigational drug

--Patient Characteristics--

• Age: 13 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 9 g/dL (may be posttransfusion or may receive erythropoietin)
• Hepatic: Bilirubin no greater than 1.5 times upper limit of normal (ULN); SGOT and SGPT no greater than 2 times ULN
• Renal: Creatinine no greater than 1.5 times ULN; Creatinine clearance at least 60 mL/min; Calcium no greater than 11 mg/dL (may receive agents to decrease calcium)
• Cardiovascular: No significant cardiovascular disease; No cardiac arrhythmia requiring drug or device intervention
• Neurological: No history of significant peripheral neuropathy; No significant central nervous system disease
• Other: HIV negative; Hepatitis B surface antigen negative; No concurrent serious infection requiring intravenous antibiotic therapy; No clinically significant autoimmune disease (i.e., rheumatoid arthritis); No clinically significant gastrointestinal bleeding or uncontrolled peptic ulcer disease; No history of inflammatory bowel disease; No other major illness that substantially increases the risk associated with participation in this study; Not pregnant or nursing; Effective contraception required of all fertile patients

Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States

Study chairs or principal investigators

William Edgar Carson, III,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   

Study ID Numbers:  CDR0000066482; OSU-T98-0020; NCI-T98-0020
Record last reviewed:  September 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003451
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08