Columbus, Ohio 43210


Purpose:

RATIONALE: Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma. Giving interferon alfa-2b after surgery may keep the tumor cells from growing. PURPOSE: This phase I trial is studying the side effects and best dose of interferon alfa-2b in treating patients who have undergone surgery for high-risk or metastatic melanoma.


Study summary:

OBJECTIVES: Primary - To determine whether selection of the optimal dose of interferon alfa-2b can be made using signal transduction data in patients who have undergone surgical resection for high-risk or metastatic melanoma. Secondary - To determine the tolerability of this drug when administered at an optimized dose, in terms of toxicities observed and the ability of patients to receive a full year of therapy. - To determine the transcription of a panel of IFN-α-induced genes previously identified by microarray analysis using real-time RT PCR in order to evaluate the correlation between STAT1 phosphorylation and IFN-α gene regulation. - To evaluate the effect of dose reduction on IFN-α gene expression by microarray analysis using peripheral blood mononuclear cell samples. - To define the clinical role of tumor sensitivity to IFN-α by systematically evaluating cellular levels of Jak-STAT signaling intermediates using tumor biopsy samples. OUTLINE: This is a dose-reduction study followed by a dose-optimization study. Patients receive interferon alfa-2b (IFN-α-2b) IV 5 days a week for 4 weeks in the absence of disease progression or unacceptable toxicity. Patients then receive standard-dose IFN-α-2b subcutaneously (SC) 3 days a week for 1-2 months*. Patients who tolerate standard-dose IFN-α-2b then receive reduced doses of IFN-α-2b SC 3 days a week for up to 8 weeks. Once the optimized dose has been determined, patients receive IFN-α-2b at the optimized dose SC 3 days a week for up to 11 months** in the absence of disease progression or unacceptable toxicity. NOTE: *The first 10 patients enrolled on the study receive standard-dose IFN-α-2b SC for 2 months. All subsequent patients receive standard-dose IFN-α-2b SC for 1 month. NOTE: **Total treatment time with SC IFN-α-2b. Blood samples are collected periodically during study treatment to obtain peripheral blood mononuclear cells (PBMCs) for correlative laboratory studies. Samples are analyzed for the presence of P-STAT1 and P-STAT2 within PBMCs, T cells, and NK cells by dual parameter flow cytometry. Levels of STAT1 and STAT2 (i.e., nonphosphorylated form) are measured to determine the degree of inter-patient variation and the effects of IFN-α on the expression of these species. Signal transduction is evaluated at each INF-α-2b dose level to determine whether a significant decrease in Jak-STAT activation has been achieved as a result of the dose reduction. PBMCs are also analyzed for induction of selected IFN-α-regulated genes by real-time RT PCR and for gene expression by microarray analysis. Previously collected paraffin-embedded tumor tissue samples are analyzed for levels of Jak-STAT signaling intermediates by immunohistochemistry. After completion of study therapy, patients are followed every 3-6 months for up to 2 years.


Criteria:

DISEASE CHARACTERISTICS: - Diagnosis of melanoma, meeting one of the following criteria: - High-risk cutaneous or nodal disease (Breslow thickness > 4 mm or lymph node disease) - Metastatic disease - Candidate for adjuvant interferon alfa-2b - Has undergone successful surgical resection of high-risk melanoma OR complete resection of metastatic disease within the past 90 days - No evidence of persistent or recurrent disease, as determined by appropriate radiologic imaging techniques PATIENT CHARACTERISTICS: - ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100% - Life expectancy > 6 months - Leukocytes ≥ 3,000/μL - ANC ≥ 1,500/μL - Platelet count ≥ 100,000/μL - Total bilirubin ≤ 2.0 mg/dL (Gilbert's disease allowed) - AST and ALT < 3 times upper limit of normal - Creatinine ≤ 1.5 mg/dL and stable OR creatinine clearance ≥ 60 mL/min - Pulse oximetry ≥ 90% on room air at rest - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception - No history of allergic reactions attributed to compounds that are similar to study drug - No known HIV positivity - No known hepatitis B surface antigen or hepatitis C antibody positivity - No immunodeficiency syndromes - Other prior malignancies allowed provided patient has been disease-free for ≥ 2 years - No concurrent uncontrolled illness including, but not limited to, any of the following: - Ongoing or active infection - Symptomatic congestive heart failure - Unstable angina pectoris - Cardiac arrhythmia - Psychiatric illness/social situation that would preclude compliance with study requirements - History of depression allowed provided the depression is controlled and the study drug is discontinued if symptoms recur - No prisoners PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 6 months since prior interferon alfa for metastatic disease - Prior interleukin-2 allowed - No prior organ allografts - No other concurrent investigational agents - No other concurrent anticancer therapy


NCT ID:

NCT00634127


Primary Contact:

Principal Investigator
William E. Carson, MD
Arthur G. James Cancer Hospital & Richard J. Solove Research Institute


Backup Contact:

N/A


Location Contact:

Columbus, Ohio 43210
United States

William E. Carson, MD
Phone: 866-627-7616
Email: william.carson@osumc.edu

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: March 16, 2018

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