Primary Disease, Prostate Cancer
Conditions
Keywords
hormone-resistant, metastatic prostatic cancer, pharmacokinetics, naïve patient
Brief 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.
Detailed description
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.
Interventions
DRUGsorafenib (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
Sponsors
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 |
| Evaluation of pharmacokinetics and pharmacodynamics of BAY43-9006 in combination with docetaxel* | after the first 24 patients |
| 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 |
| PSA response duration | at end of study |
Countries
Belgium, France
Outcome results
None listed