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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Primary Disease, Prostate Cancer

Intervention / Treatment
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* Drug: sorafenib (200 or 400mg bid) and taxotere iv


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: sorafenib (200 or 400mg bid) and taxotere iv|200 mg BID, day 3-19 cycle 1, day 2-19 other cycles 200 mg BID, day 3-21 Cycle 1, day 1-21 other cycles 400 mg BID, day 3-19 cycle 1, day 2-19 other cycles 400 mg BID, day 3-21 cycle 1, day 1-21 other cycles|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the recommended dose of BAY 43-9006 (SORAFENIB) in combination with docetaxel in hormone-refractory prostate cancer patients as first line treatment in patients with metastatic hormone refractory prostate cancer. |  | after the first 24 patients | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of pharmacokinetics and pharmacodynamics of BAY43-9006 in combination with docetaxel* |  | after the first 24 patients | 
| Toxicity and safety |  | at end of study | 
| Response rate in patients with measurable disease |  | at end of study | 
| PSA response rate |  | at end of study | 
| PSA response duration |  | at end of study | 
| Time to PSA progression (=time between treatment start and PSA progression) |  | at end of study | 
| Time to PSA progression after the last dose of docetaxel in patients with no progression after stopping docetaxel (= time between the last dose of docetaxel and PSA progression) |  | at end of study | 
| Event progression-free survival |  | at end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone-resistant, metastatic prostatic cancer, pharmacokinetics, naïve patient