pharmacokinetic study of bay43-9006 and taxotere to treat patient with prostatic cancer

Conditions: Primary Disease; Prostate Cancer

Summary: 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.

Eligibility criteria:
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.

Keywords: hormone-resistant metastatic prostatic cancer pharmacokinetics naïve patient