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Pilot Study of IFN-alpha-2b Dose Reduction With Dose Optimization

12 Years
Open (Enrolling)
Stage IA Skin Melanoma, Stage IB Skin Melanoma, Stage IIA Skin Melanoma, Stage IIB Skin Melanoma, Stage IIC Skin Melanoma, Stage IIIA Skin Melanoma, Stage IIIB Skin Melanoma, Stage IIIC Skin Melanoma, Stage IV Skin Melanoma

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Trial Information

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.

Inclusion Criteria:

- Patients must be considered a candidate for adjuvant IFN-alpha-2b therapy after
having undergone successful surgery for high-risk melanoma (Breslow thickness > 4 mm
or lymph node disease) or complete resection of metastatic disease; definitive
surgery should have been accomplished no greater than 90 days prior to start of
treatment with intravenous IFN-alpha-2b

- Patients must have completed 20 treatments of intravenous IFN-alpha-2b according to
standard practice within 2 months of beginning treatment on this study

- Patients must have not have any evidence of persistent or recurrent disease as
determined by the appropriate radiologic imaging techniques

- Patients may have received prior IFN-alpha therapy for metastatic disease, but more
than 6 months must have passed between the last dose of IFN-alpha therapy for
metastatic disease and the first dose of intravenous IFN-alpha-2b; patients who have
had prior interleukin (IL)-2 are eligible for this study

- Patients may have received radiation therapy after intravenous IFN-alpha-2b; they may
begin subcutaneous dosing of IFN-alpha-2b on this study after the radiation therapy
has been completed; the patient may initiate dose reductions after the last radiation
treatment as long as the appropriate amount of time has passed

- Life expectancy of greater than 6 months

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 70%)

- Leukocytes >= 3,000/ul

- Absolute neutrophil count >= 1,500/ul

- Platelets >= 100,000/ul

- Total bilirubin =< 2.0 (Gilbert's disease permitted)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT])
< 3 x institutional upper limit of normal

- Creatinine =< 1.5 and stable OR

- Creatinine clearance >= 60 mL.min/1.73 m^2 for patients with creatinine levels above

- Pulse oximetry >= 90% on room air at rest

- Serum pregnancy test negative

- The effects of interferon alpha-2b on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason, and because interferons are known to
be teratogenic, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation; should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately

- All patients must be informed of the investigational nature of this study and must
provide written informed consent in accordance with institutional and federal
guidelines; a copy of the informed consent document signed by the patient must be
given to the patient

Exclusion Criteria:

- Patients may not be receiving any investigational agents

- History of allergic reactions attributed to compounds that are similar to interferon

- Patients known to be positive for human immunodeficiency virus (HIV), Hepatitis B
surface antigen (HbsAg) or hepatitis C antibody

- Patients with organ allografts or immunodeficiency syndromes

- Patients with prior malignancies may participate provided they have been free of
disease for at least 2 years except for tumors with a negligible risk for metastasis
or death, such as adequately controlled basal cell carcinoma or squamous-cell
carcinoma of the skin or carcinoma in situ of the cervix

- Uncontrolled inter-current illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements; a history of depression in and of itself is not an exclusion to
going participating provided the patient and physician believe the depression is
controlled and the patient will discontinue the IFN-alpha should symptoms recur

- Pregnant women are excluded from this study because interferon alpha-2b is an agent
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with IFN-alpha, breastfeeding should be discontinued if the
mother is treated with IFN-alpha

- Prisoners will be excluded due to the need for multiple timed visits

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Selection of the optimal recombinant interferon alfa-2b dose using signal transduction data

Outcome Description:

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.

Outcome Time Frame:

up to 4 weeks

Safety Issue:


Principal Investigator

William Carson, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

April 2008

Completion Date:

Related Keywords:

  • Stage IA Skin Melanoma
  • Stage IB Skin Melanoma
  • Stage IIA Skin Melanoma
  • Stage IIB Skin Melanoma
  • Stage IIC Skin Melanoma
  • Stage IIIA Skin Melanoma
  • Stage IIIB Skin Melanoma
  • Stage IIIC Skin Melanoma
  • Stage IV Skin Melanoma
  • high risk melanoma
  • lymph node disease
  • Melanoma
  • Skin Neoplasms



Ohio State University Medical CenterColumbus, Ohio  43210