A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).
A Phase I Study Of Peginterferon Alfa-2b (PEG-INTRON) With Sorafenib (Nexavar) In Patients With Unresectable Or Metastatic Clear Cell Renal Carcinoma (RCC).
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.
OBJECTIVES:
Primary
Secondary
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.
Inclusion Criteria:
PATIENT CHARACTERISTICS:
ECOG performance status 0-1
Life expectancy > 6 months
Good/intermediate Motzer prognostic status
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 10.0 g/dL
Total bilirubin ≤ 2.0 mg/dL
AST and ALT < 2.5 times normal
Creatinine ≤ 1.8 mg/dL OR creatinine clearance > 50 mL/min
Calcium < 12 mg/dL (when corrected for serum albumin)
INR < 1.5 times upper limit of normal
Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% by 2D echo
Pulse oximetry ≥ 90% at rest on room air
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
No evidence of bleeding diathesis
No uncontrolled coagulation disorders
No active infections requiring IV antibiotics
No known HIV, hepatitis C, or hepatitis B
No autoimmune disease requiring ongoing therapy
No requirement for adrenal replacement
No angina (controlled or uncontrolled)
No uncontrolled hypertension
No history of other major medical illnesses including, but not limited to, any of the following:
No other prior malignancy except for previously treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 3 years
No significant psychiatric disease that, in the opinion of the principal investigator, would preclude giving adequate informed consent or render immunotherapy unsafe
PRIOR CONCURRENT THERAPY:
No prior treatment for RCC except sunitinib malate
No prior systemic treatment for metastatic disease (other than sunitinib malate)
No prior organ allografts
At least 2 weeks since prior laparoscopic/robotic surgery
At least 4 weeks since prior open nephrectomy
More than 4 weeks since prior and no concurrent radiotherapy or other surgery
More than 4 weeks since prior systemic steroids
More than 2 weeks since prior topical, injected, or inhaled steroids
No concurrent steroid therapy
No concurrent Hypericum perforatum (St. John's wort)