Metastatic Prostate Cancer
Conditions
Keywords
prostate, cancer, metastatic hormone-naive, radiotherapy, abiraterone acetate, docetaxel
Brief summary
This is a multi-center phase III study to compare the clinical benefit of androgen deprivation therapy with or without docetaxel with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer.
Detailed description
Eligible patients can be randomize in the trial after his consent form has been signed, and after all inclusion and non-inclusion criteria have been checked. The randomisation will result in the allocation of arm A (ADT +docetaxel), arm B (ADT +docetaxel +Abiraterone), arm C (ADT +docetaxel +radiotherapy) or arm D (ADT +docetaxel +Abiraterone +radiotherapy) in a 1:1:1:1 ratio. The randomization will be stratified (by minimization) according to: * enrolment center, * performance status (0 vs. 1-2) * disease extent: lymph nodes only vs. bone (with or without lymph nodes) vs. presence of visceral metastases. CRPC is defined by cancer progression (either a confirmed PSA rise or a radiological progression) with serum testosterone being at castrated levels (\<0.50 ng/mL). When the CRPC stage is reached, castration (either LHRH agonist or LHRH antagonist) will be maintained in all patients. Investigators will be free to manage patients reaching CRPC at their discretion (using for example docetaxel, zoledronic acid, denosumab, sipuleucel-T, radium-223, cabazitaxel, etc) according to local uses and guidelines. Abiraterone may be used in arm A and C if abiraterone has become the standard treatment for CRPC when this stage is reached.
Interventions
DRUGabiraterone acetate
abiraterone 1000mg/day (4 tablets of 250 mg (PO) per day) + prednisone 5mg bid
RADIATIONradiotherapy
74 Gy in 37 fractions 3D-Conformal RT or Intensity Modulated RT (IMRT)
OTHERAndrogen Deprivation Therapy
The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy
DRUGDocetaxel
6 cycles at 75mg/m²/cycle, one cycle every 3 weeks
Sponsors
Janssen-Cilag Ltd.
European Organisation for Research and Treatment of Cancer - EORTC
Ipsen
Sanofi
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed adenocarcinoma of the prostate, 2. Metastatic disease documented by a positive bone scan (any technique) or CT scan or an MRI. For patients with nodal metastases only, only patients with extra-pelvic enlarged lymph nodes (lymph nodes located above the iliac bifurcation) can be included if they have either: o At least one extra-pelvic lymph node ≥ 2 cm or extra-pelvic lymph node (s) ≥ 1 cm if the patients also have at least one pelvic lymph node ≥ 2 cm 3. Patients with ECOG ≤ 1 (patient with PS 2 due to bone pain can be accrued in the trial), 4. Life expectancy of at least 6 months, 5. Male aged ≥ 18 years old and ≤ 80 years old , 6. Hematology values: * Hemoglobin ≥ 10.0 g/dL, * Platelet count ≥ 100,000/mL, * Neutrophil ≥ 1500 cells/mm³ 7. Biochemistry values: * Renal function: Serum creatinine \< 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min, * Serum potassium ≥ 4 mmol/L, * Liver function: * Serum bilirubin ≤ 1.5 x ULN (except for patients with documented Gilbert's disease), * AST and ALT ≤ 1.5 x ULN (and ≤ 5 ULN in case of liver metastases), * ALK-P ≤ 2.5 x ULN (in case of bone metastasis, ALK-P\<1000U/L if bilirubin is normal) 8. Patients must have received ADT for a maximum of 3 months before randomization and there must be a minimum of 6 weeks between the start of ADT and the start of Docetaxel, 9. Patients willing and clinically fit to receive Docetaxel which is defined by the following : * Patients respecting all inclusion and
Exclusion criteria
And * Patients with no contraindication to docetaxel according to the SmPC of the drug And * Patients presenting all medical requirements to receive docetaxel according to the investigator's opinion. 10. Patients might have received previous radiation therapy directed to bone lesions, 11. Patients able to take oral medication, 12. Patients who have received the information sheet and signed the informed consent form, 13. Male patients who will receive Docetaxel and/or Abiraterone acetate and have partners of childbearing potential and/or pregnant partners must use a method of birth control in addition to an adequate barrier protection (condoms) as determined to be acceptable by the study doctor during the treatment period and for 4 weeks after the last dose of abiraterone acetate and/or for 6 months after the last dose of Docetaxel 14. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures, 15. Patients with a public or a private health insurance coverage, according to local laws for participation in clinical trials.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | 7.5 years after the first inclusion | Overall and radiographic progression-free survival in patients with metastatic hormone-naïve prostate cancer treated by androgen deprivation therapy and docetaxel |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Genitourinary event-free survival (S-GU-EFS) | 9.5 years after the first inclusion | — |
| Prostate cancer specific survival | 9.5 years after the first inclusion | — |
| Time to next skeletal-related event | 9.5 years after the first inclusion | — |
| PSA response rate | 9.5 years after the first inclusion | — |
| Prospective correlative study of PSA response/progression at 8 months after initation of ADT | 9.5 years after the first inclusion | — |
| Time to pain progression | 9.5 years after the first inclusion | will be evaluated by questionnaires |
| Castration resistance-free survival (CRFS) | 9.5 years after the first inclusion | — |
| Quality of life questionnaire - Core 30 (QLQ-C30) | At baseline, 6 months, 18 months, and at the end of treatment (up to 9.5 years) | Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. |
| Functional Assessment of Cancer Therapy - Prostate (FACT-P) | At baseline, 6 months, 12 months, 18 months, and at the end of treatment (up to 9.5 years) | The FACT-P is a self-assessment questionnaire to estimate the health-related quality of life in men with prostate cancer. This questionnaire, composed of 39 items consists of four subscales: Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), Functional Well-Being (7 items), and prostate cancer subscale (12 items). Subscales are rated on 5-point Likert-type scale (from 0 = Not at all to 4 = Very much). For all subscales, a higher score represents better quality of life. |
| Toxicity (with a specific focus on the use of long-term low-dose steroids) | Throughout study completion, up to 9.5 years | The National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = death) determined by the investigator, will make it possible to assess the severity of the disorders. |
| Changes in bone mineral density | At baseline, 6 months, 12 months, and 24 months | X-rays are used to measure how many grams of calcium and other bone minerals are packed into a segment of bone |
| Correlation of biomarkers with outcome | 9.5 years after the first inclusion | Correlation of biomarkers with outcome, including the prognostic and predictive value on OS, rPFS and CRFS of a neuro-endocrine differentiation of the prostate cancer in the pathological specimen. |
| Time to chemotherapy for CRPC | 9.5 years after the first inclusion | — |
Countries
Belgium, France, Ireland, Italy, Romania, Spain, Switzerland
Outcome results
None listed