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. Giving sorafenib before and
after surgery may be an effective treatment for kidney cancer.
PURPOSE: This phase II trial is studying how well sorafenib works in treating patients who
are undergoing surgery for metastatic kidney cancer.
- Determine the efficacy of neoadjuvant sorafenib, in terms of response rate, in patients
with metastatic renal cell carcinoma who are undergoing cytoreductive nephrectomy.
- Determine the toxic effects of this drug in these patients.
- Determine the intraoperative and peri/postoperative safety of this drug in these
- Determine the time to progression, duration of response, and overall survival of
patients treated with this drug.
OUTLINE: This is a non-randomized study. Patients are sequentially assigned to 1 of 3
- Group 1: Patients undergo cytoreductive nephrectomy on day 1. Patients then receive
oral sorafenib twice daily on days 15-84.
- Group 2: Patients receive oral sorafenib twice daily on days 1-7. Patients undergo
cytoreductive nephrectomy on day 8. Patients then receive oral sorafenib twice daily on
- Group 3: Patients receive oral sorafenib twice daily on days 1-28. Patients undergo
cytoreductive nephrectomy on day 29. Patients then receive oral sorafenib twice daily
on days 43-84.
In all groups, patients with stable or regressing disease continue to receive oral sorafenib
twice daily for up to 1 year in the absence of disease progression or unacceptable toxicity.
Some patients may continue treatment for longer than 1 year at the discretion of the
After completion of study treatment, patients are followed every 2 months.
PROJECTED ACCRUAL: A total of 45 patients (15 per treatment group) will be accrued for this
study within 1 year.
1. Patients with histologically or cytologically confirmed metastatic clear cell RCC who
are eligible for cytoreductive nephrectomy as agreed upon by Medical Oncology and
Urology team members. Patients with metastatic disease eligible for cytoreductive
nephrectomy should have the following characteristics: resectable primary tumor (no
gross adjacent organ invasion, no or minimal abdominal lymphadenopathy, no or minimal
inferior vena caval involvement), bulk of metastatic disease within the primary
tumor, absence of multiple liver metastases, no more than 2 organ sites involved with
2. 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.
3. Age >/= 18 years. Because no dosing or adverse event data are currently available on
the use of BAY 43-9006 in patients < 18 years of age, children are excluded from this
4. ECOG performance status </= 1.
5. Pts must have adequate organ & marrow function within 14 days as defined: (1)
absolute neutrophil count >/= 1,500/uL; (2) platelets >/= 100,000/uL; (3) Hgb >9.0
g/dL (may be transfused or receive epoetin alfa [e.g., Epogen®] to maintain or exceed
this level); (4) total bilirubin </= 2.0 mg/dl; (5) albumin >3.0 g/dL; (6) serum
creatinine </= 2.0 mg/dl; (7) AST(SGOT) &/or ALT (SGPT) </= 2.5 X institutional upper
limit of normal for subj. w/o evidence of liver metastases; (8) AST(SGOT) &/or ALT
(SGPT) </= 5 X institutional upper limit of normal for subjects w/ documented liver
6. Female patients of childbearing potential must have a normal plasma beta human
chorionic gonadotropin (bHCG) within 24 hours prior to enrolling in the study due to
the possible teratogenic effect. However, patients will be eligible if their BHCG
elevation is due to tumor production.
7. Patients of child fathering or childbearing potential must agree to practice a form
of medically acceptable birth control while on study.
8. 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.
9. Patients must have ability to comply with study and/or follow-up procedures.
10. Prior biopsy material (blocks or unstained slides) must be available for comparison
1. 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.
2. Patients must not have received any systemic anticancer therapy or radiotherapy
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.
3. Patients must not be scheduled to receive another experimental drug while on this
study. Patients are permitted to be on concomitant bisphosphonates.
4. Patients who are incapable of swallowing pills are excluded from the study.
5. Patients must not have a primary brain tumor, any brain metastases, leptomeningeal
disease, seizure disorders not controlled with standard medical therapy, or history
6. Patients must not have active acute infections that could be worsened by anticancer
therapy or interfere with this study.
7. Patients must not have clinically significant cardiovascular disease, recent
myocardial infarction(i.e. last 6 months), (unstable angina), New York Heart
Association (NYHA) Grade II or greater congestive heart failure, serious cardiac
dysrhythmia requiring medication, or peripheral vascular disease (Grade II or
8. 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.
9. Patients with uncontrolled hypertension > 140/90 are excluded from the study.
10. Patients must not have any history of bleeding diathesis. Patients must not be on
therapeutic anticoagulation. Prophylactic anticoagulation (i.e. low dose coumadin) of
venous or arterial access devices is allowed provided that the requirements for PT,
INR or PTT are met.
11. 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.
12. 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.