A prospective randomised phase III study of androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer. - GETUG-AFU 21

• Register: EUCTR
• Last refreshed on: 9 March 2015
• Main ID: EUCTR2012-000142-35-IT
• Date of registration: 29/10/2014
• Prospective Registration: Yes
• Primary sponsor: UNICANCER
• Public title: A prospective randomised phase III study of androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer. - GETUG-AFU 21
• Scientific title: A prospective randomised phase III study of androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate and prednisone in patient with metastatic hormone-naïve prostate cancer. - GETUG-AFU 21
• Date of first enrolment: 22/12/2014
• Target sample size: 916
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000142-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate Number of treatment arms in the trial: 4

Countries of recruitment

Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Spain, Switzerland, United Kingdom

Contacts

• Name: Corinne
• Affiliation: UNICANCER

• Name: Corinne
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the prostate,
2. Metastatic disease documented by positive bone scan or CTscan or 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
o 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,
6. Hemoglobin = 10.0 g/dL,
7. Platelet count = 100,000/µL,
8. Renal function: serum creatinine < 1.5 x ULN or a calculated creatinine clearance = 60 mL/min,
9. Serum potassium > 4 mmol/L,
10. Liver function: Serum bilirubin = 1.5 x ULN (except for patients with documented Gilbert’s disease); AST and ALT = 2.5 x ULN (and = 5 ULN in case of liver metastases),
11. Patients might have received a maximum of 3 months of androgen deprivation therapy (ADT) before randomization,
12. Patients might have received previous radiation therapy directed to bone lesions, as far as it is terminated by the time of randomization,
13. Patients able to take oral medication,
14. Patients who have received the information sheet and signed the informed consent form,
15. Male patients who are receiving the study treatment and have partners of childbearing potential and/or pregnant partners are advised to use a method of birth control in addition to 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 the study treatment,
16.Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures,
17.Patients with a public or a private health insurance coverage, according to the local laws for partipation in clinical trials
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 458
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 458

Exclusion criteria:
1. Patients with previous local treatment directed to the prostate primary cancer (radiotherapy, brachytherapy, radical prostatectomy, or other). A previous trans-urethral resection of the prostate (TURP) is allowed,
2. Prior cytotoxic chemotherapy or biological therapy for the treatment of CRPC,
3. Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone twice daily,
4. Active infection or other medical condition for which prednisone/prednisolone (corticosteroid) use would be contraindicated,
5. Previously treated with ketoconazole for prostate cancer for more than 7 days,
6. Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of randomization,
7. Uncontrolled hypertension (systolic BP = 160 mmHg or diastolic BP = 95 mmHg),
8. Patients with a history of hypertension that is not controlled by anti-hypertensive treatment,
9. Severe hepatic impairment or moderate hepatic impairment (Child – Pugh class C or B)
10. Active or symptomatic viral hepatitis or chronic liver disease (except Gilbert’s disease),
11. History of pituitary or adrenal dysfunction,
12. Pathological finding consistent with small cell carcinoma of the prostate,
13. Clinically known significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart association (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of < 50% at baseline,
14. Atrial Fibrillation, or other cardiac arrhythmia requiring therapy,
15. Other malignancy, except non-melanoma skin cancer, with a = 30% probability of recurrence within 24 months,
16. Known allergies, hypersensitivity or intolerance to the study drugs or excipients,
17. Administration of an investigational therapeutic within 30 days of M1 D1,
18. Patients already included in another therapeutic trial involving an experimental drug,
19. Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial. Those conditions should be discussed with the patient before registration in the trial,
20. Individual deprived of liberty or placed under the authority of a tutor.


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

metastatic hormone-naïve prostate cancer
MedDRA version: 17.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Abiraterone Acetate
Pharmaceutical Form: Tablet
CAS Number: 154229-18-2
Other descriptive name: ABIRATERONE ACETATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: _

Main Objective: To assess the efficacy of androgen deprivation therapy with or without local radiotherapy with or without abiraterone acetate and prednisone in terms of overall survival (OS) and progression-free survival (PFS) in patient with metastatic hormone-naïve prostate cancer.

Primary end point(s): The primary endpoints of this study are overall survival (OS) and CRPC progression-free survival (PFS).
Overall survival (OS) is defined as the time from randomization to the time of death from any cause and progression-free survival (PFS) is defined as the time from randomization to the castrate-resistant stage or death of any cause.
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).
A PSA rise is defined by an increased serum PSA on 2 different measurements, confirmed on a third measurement (measurement A

Secondary Objective: •PSA response rate
•Prospective correlative study of PSA response/progression at 8 months
•Radiological progression-free survival
•Prostate cancer specific survival
•Time to pain progression
•Time to next skeletal-related event
•Time to chemotherapy
•Time to severe local symptoms
•Toxicity (with a specific focus on the use of long-term low-dose steroids)

Secondary Outcome(s)

Secondary end point(s): •The PSA response rate will be defined by an undetectable serum PSA level at 8 months,
•The prospective correlative study of PSA response/progression will be evaluate at 8 months,
•The radiological progression-free survival will be defined by RECIST criteria v1.1 or by the appearance of at least 2 new bone metastases on bone scan according to modified PCWG2 criteria or death,
•The prostate cancer-specific survival will be calculated from the date of randomization to the date of the death due to prostate cancer,
•The time to pain progression will be evaluated by questionnaires,
•The time to next skeletal-related event will be defined by even a fracture or bone pain requiring radiation therapy or spinal cord compression or preventive surgery to the bones. Events will be evaluated by investigators. No systematic X-Ray will be perform,
•The time to chemotherapy will be calculated from the date of randomization to the date of the introduction of chemotherapy treatment,
•The time to severe local symptoms (grade 3 and 4 events) related to tumor progression and/or radiotherapy long term side effets will be evaluated according to NCI-CTCAE v4.0,
•The impact of the radiotherapy protocol on outcome (PFS and local symptoms),
•Toxicity (with a specific focus on the use of long-term low-dose steroids) will be evaluated according to NCI-CTCAE v4.0,

Timepoint(s) of evaluation of this end point: _

Secondary ID(s)

UC-0160/1105

2012-000142-35-FR

Source(s) of Monetary Support

JANSSEN-CILAG