Clinical trial NCT00405210: Pharmacokinetic Study of BAY43-9006 and Taxotere to Treat Patient With Prostatic Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Disease
Prostate Cancer
Keywords: hormone-resistant
metastatic prostatic cancer
pharmacokinetics
naïve patient
Lead sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Sponsor class: OTHER
First posted: 2006-11-29
Enrollment: 38
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: after the first 24 patients
Secondary outcomes:
measure: Evaluation of pharmacokinetics and pharmacodynamics of BAY43-9006 in combination with docetaxel*
timeFrame: after the first 24 patients
measure: Toxicity and safety
timeFrame: at end of study
measure: Response rate in patients with measurable disease
timeFrame: at end of study
measure: PSA response rate
timeFrame: at end of study
measure: PSA response duration
timeFrame: at end of study
measure: Time to PSA progression (=time between treatment start and PSA progression)
timeFrame: at end of study
measure: 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)
timeFrame: at end of study
measure: Event progression-free survival
timeFrame: at end of study
Other outcomes:
Locations:
city: Ottignies
country: Belgium
facility: St Pierre
state: Brabant Wallon
city: Brussels
country: Belgium
facility: Cliniques Universitaires St Luc
state: Brussels Capital
city: Charleroi
country: Belgium
facility: Notre Dame et Reine Fabiola
state: Hainaut
city: Yvoir
country: Belgium
facility: Clinique Universiataire de Mont Godinne
state: Namur
city: Namur
country: Belgium
facility: Sainte Elisabeth
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
Study officials:
affiliation: Cliniques Universitaires St Luc -UCL
name: Jean-Pascal H Machiels, Prof
role: STUDY_DIRECTOR
References: