Pilot Study of IFN-alpha-2b Dose Reduction With Dose Optimization
I. To determine whether selection of the optimal IFN-alpha-2b (recombinant interferon
alfa-2b) dose can be made using signal transduction data.
I. To determine the tolerability of adjuvant IFN-alpha-2b administered at an optimized dose
in terms of the toxicities that are observed and the ability of patients to receive a full
year of therapy.
II. The transcription of a panel of IFN-alpha-induced genes previously identified by
microarray analysis will be determined by Real-Time reverse transcriptase-polymerase chain
reaction (RT PCR) in order that the correlation between signal transducer and activator of
transcription 1 (STAT1) phosphorylation and IFN-alpha gene regulation can be evaluated.
III. Microarray analysis of patient peripheral blood mononuclear cells (PBMCs) will be used
to evaluate the effect of dose-reduction on IFN-alpha gene expression.
IV. In order to define the clinical role of tumor sensitivity to IFN-alpha, patient tumor
biopsies taken prior to the administration of IFN-alpha will be systematically evaluated for
cellular levels of janus kinase (Jak)-STAT signaling intermediates.
Patients receive recombinant interferon alfa-2b subcutaneously (SC) thrice weekly. Treatment
continues for 11 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 2 years.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Selection of the optimal recombinant interferon alfa-2b dose using signal transduction data
Accomplished through a one-sided confidence interval on the difference between observed response at a lower dose and the observed response at the standard dose. If we cannot declare non-inferiority for a dose, the patient will go back to the lowest dose at which non-inferiority can be claimed.
up to 4 weeks
William Carson, MD
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|