Safety and Toxicity Study of Sorafenib in Patients With Kidney Cancer
Condition: Carcinoma, Renal Cell; Kidney Disease; Kidney Cancer
MeSH terms: Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Kidney Diseases
Intervention: Sorafenib
Intervention description: Sorafenib administered in escalating 28-days cycles (400, 600 and 800 mg BID)
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically- or cytologically-confirmed metastatic or unresectable renal cell
             carcinoma (RCC).

          2. must have a component of conventional clear cell renal carcinoma.

          3. No more than one prior systemic therapy.

          4. No prior vascular endothelial growth factor receptor agents.

          5. 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.

          6. 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.

          7. Measureable disease by RECIST criteria

          8. Karnofsky performance status at least 70% or ECOG not more than 2

          9. Ability to give written informed consent

         10. At least 18 years old

         11. Negative pregnancy test within 7 days of Day 1 dosing (female subjects of childbearing
             potential)

         12. Sexually active fertile subjects must agree to use an accepted method of contraception
             during the course of the study for 3 months thereafter.

         13. ANC at least 1,500/uL

         14. Platelet count at least 100,000/uL

         15. AST/ALT not more than 2.5 times the upper limit of normal (ULN)

         16. Alkaline phosphatase not more than 2.5 x ULN

         17. Serum bilirubin not more than 1.5 x ULN

         18. Amylase/Lipase within normal range

         19. Urinalysis not more than 1+ protein

         20. Serum creatinine not more than 1.5 x ULN

         21. No active ischemia by ECG

         22. Echocardiogram or MUGA ejection fraction at least 40%

        Exclusion Criteria:

          1. Ongoing hemoptysis

          2. Cerebrovascular accident within 12 months

          3. Peripheral vascular disease with claudication on less than 1 block

          4. History of clinically significant bleeding

          5. Malignancy with true papillary/sarcomatoid features without any clear cell component

          6. Chromophobe

          7. Oncocytoma

          8. Collecting duct tumors

          9. Transitional cell carcinoma

         10. Deep venous thrombosis or pulmonary embolus within one year of consent

         11. 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

         12. Subjects with evidence of current central nervous system (CNS) metastases

         13. MRI or CT scan of the brain (with contrast, if possible) within 28 days prior to Day 1
             dosing

         14. Significant cardiovascular disease defined as congestive heart failure (New York Heart
             Association Class II, II or IV)

         15. Angina pectoris requiring nitrate therapy

         16. Myocardial infarction within the last 6 months

         17. Uncontrolled hypertension (defined as blood pressure at least 160 mmHg systolic or at
             least 90 mmHg diastolic on medication)

         18. Ongoing requirement for systemic corticosteroid therapy (except replacement therapy
             for adrenal insufficiency). Topical and/or inhaled steroids are allowed.

         19. Uncontrolled psychiatric disorder

         20. Delayed healing of wounds, ulcers, and/or bone fractures

         21. 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)

         22. Pregnant

         23. Currently lactating

         24. Currently using St John's Wort (an herb)