Phase I/II Study to Evaluate the Ability of Sorafenib in Overcoming Resistance to Systemic Chemotherapy in Androgen-independent Prostate Cancer (AIPC)
- Age > 18 years old
- ECOG Performance Status 0, 1, or 2.
- Patients with a known diagnosis of prostate cancer regardless of their Gleason grade.
- Patients have AIPC.
- Adequate bone marrow, liver and renal function as assessed by:
- Hemoglobin > 9.0 g/dl
- ANC > 1,000/mm3
- Platelet count > 75,000/mm3
- Total bilirubin < 1.5 x ULN
- ALT and AST < 2.5 x the ULN (< 5 x ULN for patients with liver involvement). INR <
1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation treatment
with an agent such as warfarin or heparin may be allowed to participate.
- Creatinine < 1.5 x ULN
- Transfusions and the use of growth factors (for red and white cells) are allowed
- Patients must have received either docetaxel or mitoxantrone as the chemotherapy
- Ability to understand and willingness to sign a written informed consent. A signed
informed consent must be obtained prior to any study specific procedures.
- Patients must have progressed while receiving systemic chemotherapy for AIPC.
Patients could have progressed within 12 weeks of their last systemic chemotherapy
administration. The definition of progression is defined as follows:
- 1-For patients who are receiving systemic chemotherapy (one criteria is
- Increase in PSA by 25% or more than the previous value. This should be repeated
within 3 weeks (while patient is off chemotherapy) to confirm that the PSA did
- For patients with visceral disease, radiographic evidence of progression by
standard RECIST criteria (regardless of the PSA value).
- For patients with bone only disease, progression on a whole body bone scan (2 or
more new lesions) is sufficient to fulfill the definition of progressive
disease, regardless of PSA value or the visceral disease status.
- 2-For patients who have received chemotherapy previously (Both criteria are
- Not more than 12 weeks have elapsed since last chemotherapy administration
- Either biochemical progression (25% increase in PSA that is confirmed with a
repeat analysis within 3 weeks), OR radiographic progression (RECIST criteria
for visceral disease patients OR 2 or more lesions on a whole body bone scan)
- Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have
unstable angina or new onset angina or myocardial infarction within the past 6
- Known brain metastasis. Patients with neurological symptoms must undergo a CT scan or
MRI of brain to exclude brain metastasis.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Patients with
history of chronic and well controlled atrial fibrillation are allowed.
Beta-blockers, calcium channel blockers, or digoxin are not considered
- Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
pressure > 90 mmHg, despite optimal medical management.
- Sorafenib is contraindicated in patients with known severe hypersensitivity to
sorafenib or any of the excipients.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Active clinically serious infection > CTCAE Grade 2.
- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months.
- 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 uncontrolled 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.