View Clinical Trial (Medical Research Study)
A Pilot Study Of Interferon-Alpha-2B Dose Reduction With Dose Optimization
| City: |
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Columbus |
| State: |
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Ohio |
| Zip Code: |
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43210 |
| Conditions: |
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Melanoma (Skin) |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT00634127 |
| Primary Contact: |
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Principal Investigator
William E. Carson, MD
Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
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| Backup Contact: |
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N/A |
| Location Contact: |
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Columbus, Ohio 43210
United States
William E. Carson, MD
Phone: 866-627-7616
Email: william.carson@osumc.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 18, 2013 |
| Modifications to this listing: |
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