Phase II Double Blind Randomized Placebo Controlled Study of Sorafenib in Hormone Naïve Biochemical Recurrence of Prostate Cancer
- Histologically confirmed adenocarcinoma of the prostate
- Prior definitive treatment with radical prostatectomy and/or radiation therapy
(external beam or brachytherapy). Patients may have received post prostatectomy
radiation therapy in the adjuvant setting or for biochemical recurrence.
- Hormone sensitive prostate cancer as evidence by a serum total testosterone level
within the institution's normal range £4 weeks of registration. (Patients may have
received hormonal therapy in the adjuvant setting provided the last dose was ³ one
year from the date of enrollment.)
- All patients must have evidence of biochemical progression as determined by 3 PSA
measures. (PSA-2, PSA-1 and PSA 0) The most recent PSA value (PSA0) will serve as
the baseline. All of these PSA values must be obtained at the same reference lab
and the earliest (PSA-2) ≥ eight weeks prior to registration, but ≤ six months prior
- The most recent PSA value (PSA 0) must be drawn £ seven days of treatment and must be
greater than 0.4 ng/ml (after prostatectomy) or greater than ³1.5 ng ml (after
radiation therapy) at the time of registration.
- The patient must be at high risk for developing distant metastases by one of the
- Gleason score 8-10 on original tumor specimen or
- Prostate specific antigen doubling time (PSADT) less than nine months calculated
using the following formula PSADT in days = 0.693 (t) ln( PSA-1)-ln (PSA-2)
where t = number of days between PSA- 2 and PSA-1 PSA-1 is the most recent PSA value PSA-2
is the next most recent PSA value Ln = natural log PSADT in months = PSADT divided by 30.4
- Age > 18 years old
- ECOG Performance Status 0 or 1
- 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
- ALT and AST < 2.5 times the ULN
- Creatinine < 1.5 times ULN
- INR < 1.5 or a PT/PTT within normal limits in patients not on therapeutic
anticoagulation. Patients receiving anti-coagulation treatment with an agent
such as warfarin or heparin 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.
- Men should agree to use adequate birth control during and for at least three months
after the last administration of Sorafenib.
- Ability to understand and the willingness to sign a written informed consent. A
signed informed consent must be obtained prior to any study specific procedures.
- Consideration must be given to definitive local therapy; patient may either refuse or
not be considered a candidate.
- Therapy modulating testosterone levels (such as leuteinizing-hormone releasing
hormone agonists/antagonists and antiandrogens) for treatment of biochemical
recurrence of prostate cancer. Treatment in the neoadjuvant setting is permissible
if greater than 1 year prior to registration. Agents such as 5 alpha reductase
inhibitors, ketoconazole, megestrol acetate, systemic steroids, or herbal supplements
that are known to affect PSA (PC Spes, saw palmetto oil) are not permitted at any
time during the period that the PSA values are being collected during screening or
- Evidence of measurable or evaluable metastatic disease on chest x-ray bone scan or CT
scan performed ≤ four weeks of registration.
- Patients must not have received any other investigational agents or concurrent anti
cancer therapy £4 weeks from treatment.
- Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have
unstable angina (anginal symptoms at rest) or new onset angina (began ≤ the last 3
months) or myocardial infarction ≤ the past 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Known brain metastasis. Patients with neurological symptoms must undergo a CT
scan/MRI of the brain to exclude brain metastasis.
- 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 or C.
HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with Sorafenib. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies may be undertaken in patients
receiving combination antiretroviral therapy in the future
- Active clinically serious infection > CTCAE Grade 2.
- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks ≤ the past 6 months.
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 £4 weeks of registration.
- Any other hemorrhage/bleeding event >CTCAE Grade 3 £ 4 weeks of registration.
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy or significant traumatic injury ≤ 4 weeks of registration.
- Concurrent use of cytochrome P450 enzyme inducing antiepileptic drugs (phenytoin,
carbamazepine, and phenobarbital), rifampin or St Johns Wort. Patients must have
discontinued these medications ³14 days from starting protocol therapy
- 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.
- Prior history of cancer (except basal cell or squamous cell skin cancer) ≤ the past