A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).
- To determine the maximum tolerated dose and toxicity of PEG-interferon alfa-2b and
sorafenib tosylate in patients with unresectable or metastatic clear cell renal cell
- To determine the progression-free survival of patients treated with this regimen.
- To evaluate, in a preliminary manner, the response rate and overall survival of
patients treated with this regimen.
- To evaluate the activation of interferon-induced transcription factors in immune cell
subsets (including regulatory T cells [T regs]) using a novel flow cytometric assay and
correlate this information with clinical outcome.
- To measure circulating levels of IFN-γ and IL-5 for determination of Th1/Th2 status and
CD4+, CD25+, and FoxP3 cell number (T regs) in peripheral blood.
OUTLINE: Patients receive PEG-interferon alfa-2b subcutaneously on days 1, 8, 15, 22, 29,
36, 43, and 50. Patients also receive oral sorafenib tosylate 2-3 times daily on days 15-56
of course 1 and on days 1-56 of all subsequent courses. Courses repeat every 56 days for up
to 1 year in the absence of disease progression or unacceptable toxicity.
Blood samples are collected at baseline and periodically during study for correlative
laboratory studies. Peripheral blood mononuclear cells are analyzed for STAT proteins
(STAT1, STAT2, STAT3, STAT4, STAT5) and CD4+, CD25+, and FoxP3 regulatory T cells by flow
cytometric assays. Samples are also analyzed for the presence of VEGF, VEGFR, IFN-γ, and
IL-5 by ELISA assays; baseline expression of Jak-STAT signaling intermediates (Jak1, Tyk2,
IFNAR, and IRF9) by immunoblot analysis; and interferon-stimulated gene expression by real
time PCR and RT-PCR analysis.
After completion of study therapy, patients are followed every 3 months for 1 year, every 4
months for 1 year, every 6 months for 2 years, and then annually thereafter.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of PEG-interferon alfa-2b and sorafenib tosylate
Thomas E. Olencki, DO
Ohio State University Comprehensive Cancer Center
United States: Food and Drug Administration
|Ohio State University Comprehensive Cancer Center||Columbus, Ohio|