A Phase II Clinical Trial to Evaluate the Efficacy of BAY 43-9006 With or Without Low Dose Interferon in Metastatic Renal Cell Carcinoma

Inclusion Criteria:

- Patients with histologically or cytologically confirmed metastatic clear cell RCC

- Patients must have measurable disease, defined as a lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded) and measures >=
20 mm with conventional techniques or >= 10 mm with spiral CT scan

- ECOG performance status =< 1

- Absolute neutrophil count >= 1,500/μL

- Platelets >= 100,000/μL

- Hgb > 9.0 g/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain
or exceed this level)

- Total bilirubin =< 2.0 mg/dl

- Albumin > 3.0 g/dL

- Serum creatinine =< 2.0 mg/dl

- AST(SGOT) and/or ALT (SGPT) =< 2.5 X institutional upper limit of normal for subjects
without evidence of liver metastases

- AST(SGOT) and/or ALT (SGPT) =< 5 X institutional upper limit of normal for subjects
with documented liver metastases

- Female patients of childbearing potential must have a normal plasma beta human
chorionic gonadotropin (βHCG) within 24 hours prior to enrolling in the study due to
the possible teratogenic effect; however, patients will be eligible if their βHCG
elevation is consistent with malignancy rather than pregnancy

- Patients of child fathering or childbearing potential must agree to practice a form
of medically acceptable birth control while on study

- Patients must give written informed consent prior to initiation of therapy, in
keeping with the policies of the institution; patients with a history of major
psychiatric illness must be judged able to fully understand the investigational
nature of the study and the risks associated with the therapy; the only approved
consent is attached to this protocol

- Patients must have ability to comply with study and/or follow-up procedures

- Patients must be able to swallow pills

Exclusion Criteria:

- No prior malignancy is allowed, except for non-melanoma skin cancer, in situ
carcinoma of any site, or other cancers for which the patient has been adequately
treated and disease free for 5 years

- Patients must not have received any systemic anticancer therapy for renal cell
carcinoma; patients must not have received any radiotherapy for renal cell carcinoma
within 4 weeks prior to entering the study or those who have not recovered from
adverse events due to agents administered more than 4 weeks earlier

- Patients must not be scheduled to receive another experimental drug while on this
study; patients are permitted to be on concomitant bisphosphonates

- Patients must not have a primary brain tumor, any brain metastases, leptomeningeal
disease, seizure disorders not controlled with standard medical therapy, or history
of stroke

- Patients must not have active acute infections that could be worsened by anticancer
therapy or interfere with this study

- Patients must not have clinically significant cardiovascular disease, myocardial
infarction within the past year (unstable angina), New York Heart Association (NYHA)
Grade II or greater congestive heart failure, serious cardiac dysrhythmia refractory
to medical management, or peripheral vascular disease (Grade II or greater)

- Patients must not have uncontrolled hypertension

- Patients must not have history of other diseases, metabolic dysfunction, physical
examination finding, or clinical laboratory finding giving reasonable suspicion of a
disease or condition that contraindicates the use of an investigational drug or that
might affect the interpretation of the results of the study or render the subject at
high risk from treatment complications

- Pregnant women are excluded from this study because BAY 43-9006 is a kinase inhibitor
agent with the potential for teratogenic or abortifacient effects; because there is
an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with BAY 43-9006, breastfeeding should be discontinued if the
mother is treated with BAY 43-9006

- Patients with immune deficiency are at increased risk of lethal infections when
treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving
combination anti-retroviral therapy are excluded from the study because of possible
pharmacokinetic interactions with BAY 43-9006; appropriate studies will be undertaken
in patients receiving combination anti-retroviral therapy when indicated

- Patients must not have a clinical history of coagulopathy, bleeding diathesis or
thrombosis; patients must not be on therapeutic anticoagulation; prophylactic
anticoagulation (ie low dose warfarin) of venous access devices is allowed provided
that INR >= 1.5 is due to warfarin therapy; other patients with an INR >= 1.5 are
excluded

- Patients must not have a history of severe depression

- Concomitant treatment with rifampin, St. John's wort, and the cytochrome p450
enzyme-inducin antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital)