Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer

Study Overview
=================
Brief 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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma

Conditions
-----------------
Kidney Cancer

Intervention / Treatment
-----------------
* Drug: Sorafenib


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Sorafenib<br>The initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily. Intrapatient dose escalation will occur as defined in the table below, providing no dose limiting toxicity (Grade 3 or 4) is observed. If grade 3 or 4 toxicity is observed, delay and dose modification will occur as defined in protocol. Once dose level 3 is reached, the patient will remain at that dose as defined in following section. Dose Level 1 Day 1-28 400 mg b.i.d. Dose Level 2 Day 29-56 600 mg b.i.d. Dose Level 3 Day 57- 800 mg b.i.d. A treatment cycle will be 4 weeks. Two 4-week cycles will be administered. At the completion of two cycles (week 8), restaging will occur. Patients will continue on therapy per study protocol. | Drug: Sorafenib<br>* initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mg<br>* Other names: Nexavar;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of Intrapatient Dose Escalation of Sorafenib Tosylate | To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached. | Study completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria | from the start of the treatment until disease progression/recurrence | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
clear cell renal cell carcinoma, stage III renal cell cancer, stage IV renal cell cancer, recurrent renal cell cancer