Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer

Study Overview
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Brief Summary
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Determine time-to-progression (TTP) for an escalating dose schedule for subjects with progressive metastatic renal cell carcinoma treated with sorafenib

Detailed Description
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Sorafenib to be administered as 28-day cycles. Sorafenib dose escalation by cycle is: Cycle 1: 400 mg BID Cycle 2: 600 mg BID Cycle 3+: 800 mg BID Within subject dose escalation and maximum dose is dependent on observed tolerability. Dose escalation only occurs after acceptable tolerability is demonstrated by subject.

Official Title
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A Phase 2 Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma at Stanford University

Conditions
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Carcinoma, Renal Cell, Kidney Disease, Kidney Cancer

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically- or cytologically-confirmed metastatic or unresectable renal cell carcinoma (RCC). must have a component of conventional clear cell renal carcinoma. No more than one prior systemic therapy. No prior vascular endothelial growth factor receptor agents. Prior palliative radiotherapy in metastatic lesion(s) is permitted, provided the subject has at least one measurable and/or evaluable lesion(s) that has not been irradiated. All major surgery of any type and/or radiotherapy must be completed at least 4 weeks prior to Day 1 dosing. Patients must have recovered from surgery and/or radiotherapy toxicity prior to Day 1 dosing. Measureable disease by RECIST criteria Karnofsky performance status at least 70% or ECOG not more than 2 Ability to give written informed consent At least 18 years old Negative pregnancy test within 7 days of Day 1 dosing (female subjects of childbearing potential) Sexually active fertile subjects must agree to use an accepted method of contraception during the course of the study for 3 months thereafter. ANC at least 1,500/uL Platelet count at least 100,000/uL AST/ALT not more than 2.5 times the upper limit of normal (ULN) Alkaline phosphatase not more than 2.5 x ULN Serum bilirubin not more than 1.5 x ULN Amylase/Lipase within normal range Urinalysis not more than 1+ protein Serum creatinine not more than 1.5 x ULN No active ischemia by ECG Echocardiogram or MUGA ejection fraction at least 40% Exclusion Criteria: Ongoing hemoptysis Cerebrovascular accident within 12 months Peripheral vascular disease with claudication on less than 1 block History of clinically significant bleeding Malignancy with true papillary/sarcomatoid features without any clear cell component Chromophobe Oncocytoma Collecting duct tumors Transitional cell carcinoma Deep venous thrombosis or pulmonary embolus within one year of consent Ongoing need for full-dose oral or parenteral anticoagulation. Low dose coumadin (1 mg) for maintenance of catheter patency or daily prophylactic aspirin is allowed Subjects with evidence of current central nervous system (CNS) metastases MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to Day 1 dosing Significant cardiovascular disease defined as congestive heart failure (New York Heart Association Class II, II or IV) Angina pectoris requiring nitrate therapy Myocardial infarction within the last 6 months Uncontrolled hypertension (defined as blood pressure at least 160 mmHg systolic or at least 90 mmHg diastolic on medication) Ongoing requirement for systemic corticosteroid therapy (except replacement therapy for adrenal insufficiency). Topical and/or inhaled steroids are allowed. Uncontrolled psychiatric disorder Delayed healing of wounds, ulcers, and/or bone fractures Prior malignancy (EXCEPTIONS: adequately-treated basal cell or squamous cell skin cancer or any other cancer for which chemotherapy has been completed > 5 years ago and from which the patient has been disease-free for > 5 years) Pregnant Currently lactating Currently using St John's Wort (an herb)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sorafenib<br>Cycle 1: 400 mg BID sorafenib Cycle 2: 600 mg BID sorafenib Cycle 3+: 800 mg BID sorafenib | Drug: Sorafenib<br>* Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID)<br>* Other names: Sorafenib tosylate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-progression (TTP) |  | 12 months |