A Phase II Study of the Efficacy and Tolerability of the Dose Escalation of Sorafenib in Advanced Renal Cell Cancer
- Age ≥ 18 years old.
- ECOG Performance Status 0, 1 or 2.
- Adequate bone marrow, liver and renal function as assessed by the following:
- Hemoglobin ≥ 9.0 g/dl
- Absolute neutrophil count (ANC)≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 times ULN
- and AST ≤ 2.5 times the ULN (≤ 5 x ULN for patients with liver involvement)
- Creatinine < 1.5 times ULN
- Women of childbearing potential must have a negative serum pregnancy test performed
within 7 days prior to of treatment.
- Women of childbearing potential and men must agree to use adequate contraception
(barrier method of birth control) prior to study entry and for the duration of study.
Men should use adequate birth control for at least three months after the last
administration of sorafenib.
- Ability to understand and willing to sign written informed consent. A signed
informed consent must be obtained prior to any study specific procedures.
- INR < 1.5 or a PT/PTT within normal limits unless receiving anti-coagulation
treatment with an agent such as warfarin or heparin. These patients may be allowed to
participate. For patients on warfarin, the INR should be measured prior to
initiation of sorafenib and monitored at least weekly, or as defined by the local
standard of care, until INR is stable.
- Must have histologically or cytologically confirmed renal cell carcinoma that is
metastatic (M1). Patients with unresectable primary tumor (but MO) are also
- Must have measurable disease, defined as at least 1 lesion that can be accurately
measured in at least 1 dimension. Soft tissue disease that has been radiated in the
2 months prior to registration is not assessable as measurable disease. Soft tissue
disease within a prior radiation field must have progressed to be considered
assessable. X-rays, scans or physical examinations used for tumor measurement must
have been completed within 28 days prior to registration. X-rays, scans or physical
examinations for non-measurable disease must have been completed within 42 days prior
- Patients with metastatic disease who have a resectable primary tumor and are deemed a
surgical candidate may have undergone resection and have recovered from surgery. At
least 28 days must have elapsed since surgery and must have recovered from any
adverse effects of surgery.
- May have received 1 prior immunotherapy with either interferon (IFN) and/or
Interleukin-2 (IL-2) or the combination of IFN/IL2 and only 1 prior biologic agent
(sunitinib, bevacizumab, or temsorlimus). Must have progressed during this prior
therapy. At least 14 days must have elapsed since the last treatment and must have
recovered from any adverse effects of prior therapy. May have received prior
radiation therapy. At least 21 days must have elapsed since completion of prior
radiation therapy. Must have recovered from all associated toxicities at the time of
- Cardiac disease: Congestive heart failure > class II NYHA. Must not have unstable
angina (anginal symptoms at rest) or new onset angina (began within the last 3
months) or myocardial infarction within past 6 months.
- Known brain metastasis. Patients with neurological symptoms must undergo a CT
scan/MRI of the brain to exclude brain metastasis.
- Patients who have received prior sorafenib are ineligible.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B/C.
- Active clinically serious infection > CTCAE Grade 2.
- Thrombosis or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months. Patients with renal or caval thrombosis
related to the primary renal tumor would not be excluded and are eligible.
- Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
- Serious non-healing wound, ulcer, or bone fracture.
- Evidence or history of bleeding diathesis or coagulopathy.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
- Use of St. John's Wort or rifampin (rifampicin).
- Known or suspected allergy to sorafenib or any agent given in the course of this
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem.