Pharmacokinetic Study of BAY43-9006 and Taxotere to Treat Patient With Prostatic Cancer

Open-label, Multicenter,PhaseI Trial in Order To Determine the Safety and Pharmacokinetics of BAY43-9006 in Combination With Docetaxel as First-line Treatment in Metastatic Hormone Refractory Prostate Cancer Patients

The purpose of the trial is to determine the most effective dose of BAy 46-9003 associated to taxotere for first-line treatment of patient with prostatic cancer.

BAY 43-9006 (SORAFENIB) is a novel dual-action Raf kinase and VEGFR inhibitor, which is orally available and has a favorable safety profile in patients with advanced solid tumors. This, together with the antitumor activity observed after treatment with BAY 43-9006 (SORAFENIB), provides a rationale for further evaluation in patients with advanced cancer. The recommended dose of BAY 43-9006 (SORAFENIB) for future studies is 400 mg bid as a continuous dosing schedule.

This study propose to treat patients with metastatic and hormone-refractory prostatic cancer in first intention. There is no limits of age from 18 years old. A new inhibitor of angiogenesis (Sorafenib) is associated to the standard treatment in this type of pathology.

Patients have to demonstrate radiologically a disease progression and also a progression based on increase of psa level.

The main objective is to Determine the recommended dose of BAY 43-9006 in combination with docetaxel in hormone-refractory prostate cancer patients as first line treatment in patients with metastatic hormone-refractory prostate cancer.

Inclusion Criteria:

• Signed informed consent prior to beginning protocol specific procedures.

• 18 years

• Radiologically proven presence of metastases

• Histologically/cytologically proven prostate adenocarcinoma.

• Biochemically evaluable disease

• Patients must have received prior hormonal therapy as defined below:

  • Castration by orchiectomy and/or LHRH agonists with or without
  • Antiandrogens
  • Other hormonal agents (e.g., ketoconazole, ...)

• The testosterone level should be < 50 ng/dl (10) documented disease progression defined by PSA increase. Patients must have a value of at least 5 ng/ml in addition to increasing PSA to be eligible.

• Life expectancy > 3 months

• ECOG performance status 0-2.

• Normal cardiac function.

Exclusion Criteria:

• Prior chemotherapy except estramustine phosphate.
• Prior isotope therapy (e.g., strontium, samarium).
• Prior radiotherapy to >25% of bone marrow
• Prior therapy with anti-VEGF therapy
• Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, or any other cancer from which the patient has been disease-free for >5 years.
• History or presence of central nervous system (CNS) disease (i.e. primary brain tumor, malignant seizures, CNS metastases or carcinomatous meningitis)
• Symptomatic peripheral neuropathy
• Other serious illness or medical condition the use of corticosteroids.
• Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BAY 9006.
• Major surgery with 4 weeks of study entry
• Autologous bone marrow transplant or stem cell rescue within 4 months of study entry
• Use of biologic response modifiers, such as G-CSF, within 3 weeks of study entry
• Treatment with any other anti-cancer therapy (except LHRH agonists) including any prescribed compounds and/or OTC products for the treatment of prostate cancer must be stopped.
• Treatment with drugs that are metabolized by the cytochrome P450 system (i.e warfarin sodium,…)
• Treatment with systemic corticosteroids used for reasons other than specified by the protocol must be stopped.
• Biphosphonates could not be initiated after inclusion into the protocol. At inclusion, patients receiving biphosphonates with a PSA progression could continue biphosphonates.
• Patients with reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial.
• Inadequate recovery from previous surgery, radiation, chemo-, biologic or immunotherapy
• Patients who have known hypersensitivity to the study medication
• Substance abuse, medical social, psychological conditions that may interfere with the subject's participation in the study or evaluation of study results
• Patients unable to sallow oral medications.