Clinical trial NCT00589550
Conditions: Kidney Cancer
Keywords: clear cell renal cell carcinoma stage III renal cell cancer stage IV renal cell cancer
Sponsor: Thomas Olencki
Start date: 2008-02-01; Completion date: 2009-01-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: PEG-interferon alfa-2b may interfere with the growth of tumor cells. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving PEG-interferon alfa-2b together with sorafenib may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PEG-interferon alfa-2b and sorafenib in treating patients with unresectable or metastatic kidney cancer.

Detailed description:
OBJECTIVES:

Primary

* 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 carcinoma.

Secondary

* 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.

Arms: arm 1: Peginterferon alfa-2b will be administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks.
Interventions: intervention 1: PEG-interferon alfa-2b intervention 2: Sorafenib intervention 3: gene expression analysis intervention 4: polymerase chain reaction intervention 5: reverse transcriptase-polymerase chain reaction intervention 6: flow cytometry intervention 7: immunoenzyme technique intervention 8: laboratory biomarker analysis
Intervention descriptions: intervention 1: administered SC on day 1 of each week of therapy. This will most likely be a Monday or a Tuesday. Sorafenib will be initiated on day 15 (start of week 3) of the first course and continued daily without breaks. intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None

Protocol documents: