Prostate cancer metastatic MedDRA version: 14.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ZYTIGA
Product Name: ABIRATERONE ACETATE
Pharmaceutical Form: Tablet
Sponsors
CENTRE ANTOINE LACASSAGNE
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1.Age > 18 years. 2.Histologically confirmed prostate adenocarcinoma. 3.ECOG = 2. 4.Evidence of metastatic disease by the presence of documented locoregional or distant metastases on CT scan of the abdomen and/or pelvis, or bone scintigraphy. 5.Patients who have had disease progression during or after prior docetaxel chemotherapy regimen, defined as: a.Progressive measurable disease : At least a 20% increase in the sum of the longest diameters of measurable lesions over the smallest sum observed –or- the appearance of one or more new measurable lesions as assessed by CT scan. Soft tissue disease progression defined by modified RECIST 1.1 criteria (baseline lymph node size must be = 2.0 cm to be considered target or evaluable lesion). OR b.Bone Scan Progression: appearance of 2 or more new lesions on bone scan. OR c.Increasing serum PSA level: Two consecutive increases in PSA levels documented over a previous reference value obtained at least one week apart are required. If the third PSA value is less than the second, an additional fourth test to confirm a rising PSA is acceptable. A minimum starting value of 2.0 ng/mL is required for study entry. NOTE: Androgen ablative therapy may have included either medical or surgical castration. 6.At least one prior chemotherapy regimen of docetaxel. 7.At least 28 days had to have elapsed between the withdrawal of antiandrogens and enrolment, except LH-RH agonist therapy that must be continued throughout this study for patients who were already treated by it. 8.Hormonal castration confirmed biologically (testosterone =65 years) yes F.1.3.1 Number of subjects for this age range 170
Exclusion criteria
Exclusion criteria: 1.Patients already treated with abiraterone acetate. 2.Known hypersensitivity or allergy to abiraterone or any of the excipients (see attachment 9). 3.Patients suffering from severe liver or renal impairment. 4.Any radiation within 28 days prior to study entry. 5.Patient with central nervous system (CNS) metastasis or with history of CNS metastasis. 6.Patient treated for a cancer other than prostate cancer, with the exception of basal cell carcinoma, within the past 5 years. 7.Treatment on another therapeutic clinical trial within 28 days before enrolment 8.Prior treatment with novel hormonal agents including enzalutamide, orteronel, ARN509, EPI100 and novel non hormonal treatments including cabozantinib, alpharadin. 9.Uncontrolled medical conditions such as heart failure, myocardial infarction, uncontrolled hypertension, stroke or treatment of a major active infection within 3 months of randomization, as well as any significant concurrent medical illness that in the opinion of the Investigator would preclude protocol therapy. 10.Permanent contraindication to corticosteroids. 11.Patient with history of poor compliance or current or past psychiatric conditions or severe acute or chronic medical conditions that would interfere with the ability to comply with the study protocol. 12.Patient enables to give informed consent. 13.People particularly vulnerable as defined in Articles L.1121-5 to -8 of the French Healthcare Code
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective will be to investigate the relationships between candidate-gene polymorphisms specifically related to AA pharmacology: CYP17A1, SLCO2B1 and SLCO2B3 (13 single nucleotide polymorphisms) and the clinical efficacy of AA in terms of progression-free survival. Such relationships will take into account relevant histo-prognostic factors of metastatic CRPC cancers (clinical staging, pre-treatment PSA, Gleason score) and treatment compliance. ;Secondary Objective: - To investigate relationships between the above-cited candidate-gene polymorphisms specifically related to AA pharmacology (13 single nucleotide polymorphisms) and the following pharmacological effects of AA: Biological response on PSA, Overall survival, Time-to-PSA progression, Symptomatic or clinical progression-free survival, Toxicity. To investigate the relationship between clinical end-points and genetic profile from pan-genome SNPs analyses. To investigate the link between CYP17A1 gene polymorphisms and CYP17A1 tumoral expression. To examine the possible link between the evolution of sDHEA and androstenedione circulating levels and AA pharmacodynamics. To document the frequency of potentially relevant polymorphisms of cabazitaxel (CYP3A4 and CYP3A5).;Primary end point(s): Progression-free survival will be defined as the time elapsed between treatment initiation and disease progression. Disease progression will be defined as radiographic progression in soft tissue or bone, or as PSA progression plus symptomatic progression. Radiographic progression disease assessment will be based on the use of computed tomography (CT) or magnetic resonance imaging (MRI) for Soft-tissue lesion and defined according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria or based on bone scan according to criteria adapted from the PCWG2 (Scher 2008). Biological response on PSA will be defined as a decrease of 50% in the PSA concentration from pre-treatment basel | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacogenetic analysis •Candidate-gene approach The candidate gene approach will include 13 SNPs potentially related to the pharmacodynamics of AA and 2 SNPs potentially related to cabazitaxel pharmacokinetics, all analyzed by pyrosequencing or by PCR-RFLP methods. The 13 SNPs potentially related to the pharmacodynamics of AA will concern 9 functional SNPs of the CYP17A gene (allele frequency of the rare alleles > 12%), along with 4 functional SNPs of genes involved in the membrane-transport of testosterone and dehydroepiandrosterone, SLCO2B1 and SLCO1B3 (allele frequency of the rare alleles > 20%): - Nine SNPs of CYP17A1 gene: -34 T>C (rs 743572), -362 T>C (rs 2486758), 35 T>C (rs 1004467), 137 G>A (rs 6162), 195 C>A (rs 6163), 11994 C>A (rs 4919683), 13871 A>G (rs 10883782), 15831 G>T (rs 619824) and 1243+113 T>A (rs 10883783). - Three SNPs of SLCO2B1 gene: 312Arg>Gln (rs 12422149), 3551 A>T (rs 1789693) and A>G (rs 1077858) - One SNP of SLCO1B3 gene: 112Ser>Ala (rs 4149117). The two SNPs potentially related to the variability of cabazitaxel effects will be: - One SNP of CYP3A4: variant *1B (rs 2740574), rare allele frequency = 4% - One SNP of CYP3A5: variant *3 (rs 776746), rare allele frequency = 30%. •Genome-wide approach DNA samples will also be analyzed using a genome-wide approach. However, the choice of the beadchip that will be used for this additional analysis will be defined at the end of the recruitment period, based on the most recent technological advancements. Indeed, this field presents rapid changes in technology and cost, and we need to ensure optimum utilization of the genetic material regarding analytical strategies (pan genome data quality) as well as statistical analysis (choice of the partner providing bioinformatics analysis). Analysis of circulating hormone levels The circulating levels of DHEA and androstenedione will be studied by using radioimmunoassay from a specific blood sample drawn at the | — |
Countries
France
Contacts
Public ContactLOVERA Christine
CENTRE ANTOINE LACASSAGNE
Outcome results
None listed