A Phase II Dose Escalation Study of Continuous Daily Subcutaneous Administration of Interferon Alpha-2b in Patients With Metastatic or Unresectable Clear Cell Renal Cell Carcinoma
Rationale: Interferon has long been used as a therapy for renal cell carcinoma. However,
optimal dosing schedules have not been identified and patients have been relegated to
receiving the highest possible doses for prolonged periods of time. This high-dose approach
often leads to serious adverse effects from toxicity that limits the usefulness and patient
tolerance of this treatment. No formal study has determined the relationship if any between
the maximal tolerated dose (MTD) and the biological effective dose of interferon alpha-2b.
The current study seeks to fill that gap by gathering research information about different
doses of interferon alpha-2b and correlating with measurements of JAK/STAT in the blood.
Validation of correlative studies to determine optimum biologic dosing are needed so that
therapy may be adjusted appropriately rather then the current approach of maximizing dose.
In addition, a trial of low dose daily administered interferon-2b has not been carried out
in the current era with refined histologic classification and modern CT imaging scanning.
As this therapy potentially has wide applicability, definite response rates need to be
Purpose: The purpose of this study is to assess the response rate of daily low dose
interferon-2b in patients with metastatic or unresectable clear cell renal carcinoma. The
duration of the response and overall survival will be determined in study participants. This
study will also evaluate JAK/STAT, two types of kinases or enzymes involved in an
intracellular signaling process associated with cancer growth, in peripheral blood
mononuclear cells over the course of interferon alpha-2b dose escalation. Researchers will
examine in a preliminary manner the correlation between clinical response, toxicity, and
JAK/STAT signal transduction. Progression free survival and rate of stable disease will also
be determined in a preliminary manner.
Treatment: Study participants will receive interferon alpha-2b. This drug will be
self-administered daily through injections into the skin. The dose level of interferon
alpha-2b will be increased each week into study treatments. For the first three weeks and
approximately monthly thereafter, patients will have blood drawn three hours following
interferon alpha-2b administration to measure JAK/STAT. Toxicity from study treatments will
be closely monitored in patients during clinics visits. Supportive care therapies will be
given throughout the study. Treatments will be discontinued due to disease growth or
unacceptable side effects.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Ohio State University
United States: Institutional Review Board