sorafenib in treating patients with metastatic or unresectable kidney cancer

Conditions: Kidney Cancer

Summary: rationale: sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. purpose: this phase ii trial is studying the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.

objectives: primary * evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma. secondary * determine tumor response in these patients. * determine time to progression in these patients. * determine overall survival of these patients. tertiary * collect data on angiogenesis inhibition induced by sorafenib tosylate. * collect data on immunomodulatory effects of sorafenib tosylate. outline: this is an open-label study. patients receive oral sorafenib tosylate twice daily on days 1-28. treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity. patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4 dose-limiting toxicity) until a pre-determined dose is reached. blood and urine samples are collected at baseline and periodically during study for vegf level determination. blood samples are analyzed for t4/t8, nk, cd25+, and fox p3 by flow cytometry. tumor tissue blocks or unstained slides are obtained for chemistry staining of vegf.

Eligibility criteria:
disease characteristics: inclusion criteria: * histologically or cytologically confirmed renal cell carcinoma (rcc) * must have a component of conventional clear cell rcc * predominant clear cell component ≥ 75% * metastatic or unresectable disease (measurable disease is defined as any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral ct scan or mri) * measurable or nonmeasurable disease, includes any of the following: * small lesions, longest diameter \< 20 mm by conventional techniques or \< 10 mm by spiral ct scan * bone lesions * leptomeningeal disease * ascites * pleural/pericardial effusion * lymphangitis cutis/pulmonitis * abdominal masses that are not confirmed and followed by imaging techniques * cystic lesions * irradiated lesions, unless progression is documented after radiotherapy * paraffin rcc tissue blocks or unstained slides must be obtained for future chemistry staining of vegf * karnofsky performance status 70-100% * fertile patients must use effective contraception (hormonal and/or barrier method) during and for 3 months after completion of study treatment * granulocyte count ≥ 1,500/µl * platelet count ≥ 100,000/µl * ast/alt ≤ 2.5 times upper limit of normal (uln) * alkaline phosphatase ≤ 2.5 times uln * serum bilirubin ≤ 1.5 times uln * protein ≤ 1+ by urinalysis * creatinine ≤ 1.5 times uln * at least 4 weeks since prior major surgery and/or radiotherapy and recovered * prior palliative radiotherapy for metastatic lesion(s) allowed provided there is at least one measurable and/or evaluable lesion(s) that has not been irradiated * more than 4 weeks since prior and no other concurrent anticancer therapy * concurrent continuation of bisphosphonates allowed for bone metastases prophylaxis exclusion criteria: * patients with true papillary, sarcomatoid features without any clear cell component, chromophobe, oncocytoma, collecting duct tumors, or transitional cell carcinoma are not eligible * no evidence of cns metastases * no imaging (mri or ct scan of the brain) abnormality indicative of cns metastases within past 42 days * not pregnant or nursing (negative pregnancy test) * no ongoing hemoptysis * no cerebrovascular accident within the past 12 months * no peripheral vascular disease with claudication while walking less than 1 block * no history of clinically significant bleeding * no deep venous thrombosis or pulmonary embolus within the past year * no significant cardiovascular disease, defined as nyha class ii-iv congestive heart failure, angina pectoris requiring nitrate therapy, or myocardial infarction within the past 6 months * no uncontrolled hypertension, defined as systolic bp \> 160 mm hg and/or diastolic bp \> 90 mm hg while on medication * no preexisting thyroid abnormality whose thyroid function cannot be maintained in the normal range by medication * no uncontrolled psychiatric disorder * no delayed healing of wounds, ulcers, and/or bone fractures * no currently active second malignancy except nonmelanoma skin cancer (patients are not considered to have a 'currently active' malignancy if they have completed anticancer therapy and are considered by their physician to be at less than 30% risk of relapse) * no more than one prior systemic therapy for rcc * no prior vascular endothelial growth factor receptor agents * no concurrent systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency) o topical and/or inhaled steroids allowed * no concurrent full-dose oral or parenteral anticoagulation o low-dose warfarin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin allowed * no concurrent hypericum perforatum (st. john's wort) * no concurrent ketoconazole, itraconazole, ritonavir, rifampin, or products containing grapefruit juice * no concurrent hormonal therapy or chemotherapy o concurrent hormones administered for non-disease related conditions (e.g., insulin for diabetes) allowed

Keywords: clear cell renal cell carcinoma stage iii renal cell cancer stage iv renal cell cancer recurrent renal cell cancer