A Prospective Randomised Phase III Study Of Androgen Deprivation Therapy With Or Without Docetaxel With Or Without Local Radiotherapy With Or Without Abiraterone Acetate And Prednisone In Patients With Metastatic Hormone-Naïve Prostate Cancer
Overview
- Phase
- Phase 3
- Intervention
- Androgen Deprivation Therapy
- Conditions
- Metastatic Prostate Cancer
- Sponsor
- UNICANCER
- Enrollment
- 1173
- Locations
- 77
- Primary Endpoint
- Survival
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Patients with previous definitive local treatment directed to the prostate primary cancer (radiotherapy, brachytherapy, radical prostatectomy, ultrasound, cryotherapy, or other). A previous trans-urethral resection of the prostate (TURP) and previous local treatments of metastases are allowed,
- •Prior cytotoxic chemotherapy or biological therapy for the treatment of prostate cancer,
- •Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone twice daily,
- •Active infection or other medical condition for which prednisone/prednisolone (corticosteroid) use would be contra-indicated,
- •Previously treated with ketoconazole for prostate cancer for more than 7 days,
- •Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of randomization,
- •Hypertension not controlled by an anti-hypertensive treatment (systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg; 3 consecutive measures taken 5 minutes apart),
- •Severe or moderate hepatic impairment (Child - Pugh class C or B)
- •Active or symptomatic viral hepatitis or chronic liver disease (except Gilbert's disease),
- •History of pituitary or adrenal dysfunction,
Arms & Interventions
Arm A
androgen deprivation therapy + docetaxel
Intervention: Androgen Deprivation Therapy
Arm A
androgen deprivation therapy + docetaxel
Intervention: Docetaxel
Arm B
androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Intervention: abiraterone acetate
Arm B
androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Intervention: Androgen Deprivation Therapy
Arm B
androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Intervention: Docetaxel
Arm C
Arm A + radiotherapy
Intervention: radiotherapy
Arm C
Arm A + radiotherapy
Intervention: Androgen Deprivation Therapy
Arm C
Arm A + radiotherapy
Intervention: Docetaxel
Arm D
Arm B + radiotherapy
Intervention: abiraterone acetate
Arm D
Arm B + radiotherapy
Intervention: radiotherapy
Arm D
Arm B + radiotherapy
Intervention: Androgen Deprivation Therapy
Arm D
Arm B + radiotherapy
Intervention: Docetaxel
Outcomes
Primary Outcomes
Survival
Time Frame: 9.5 years after the first inclusion
Overall and radiographic progression-free survival in hormone-naïve prostate cancer patients with low metastatic burden whatever the standard of care received
Secondary Outcomes
- PSA response rate(9.5 years after the first inclusion)
- Time to chemotherapy for CRPC(9.5 years after the first inclusion)
- Castration resistance-free survival (CRFS)(9.5 years after the first inclusion)
- 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)
- 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))
- Toxicity (with a specific focus on the use of long-term low-dose steroids)(Throughout study completion, up to 9.5 years)
- Time to next skeletal-related event(9.5 years after the first inclusion)
- Time to pain progression(9.5 years after the first inclusion)
- Correlation of biomarkers with outcome(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)
- Changes in bone mineral density(At baseline, 6 months, 12 months, and 24 months)
- 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))