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• Register: EUCTR
• Last refreshed on: 29 April 2024
• Main ID: EUCTR2012-000142-35-BE
• Date of registration: 18/08/2014
• Prospective Registration: Yes
• Primary sponsor: UNICANCER
• Public title: _
• Scientific title: A Prospective randomized phase III study of Androgen deprivation therapy with or without docetaxel with or without local radiotherapy with or without local radiotherapy with or without ABIRATERONE ACETATE and PREDNISONE in patients with Metastatic Hormone-Naïve Prostate Cancer. - GETUG AFU 21-PEACE 1
• Date of first enrolment: 01/12/2014
• Target sample size: 1173
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Netherlands, Poland, Portugal, Romania, Spain, Switzerland

Contacts

• Name: Project Leader
• Affiliation: UNICANCER

• Name: Project Leader
• Affiliation: UNICANCER

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically or cytologically confirmed adenocarcinoma of the prostate,
2. Metastatic disease documented by a positive bone scan (any technique) or a 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:
- 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/µL,
- 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); ALP = 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 are advised to 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,
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 586
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 587

Exclusion criteria:
1. 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 metastasis are allowed,
2. Prior cytotoxic chemotherapy or biological therapy for the treatment of prostate cancer,
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. Hypertension not controlled by an anti-hypertensive treatment (systolic BP = 160 mmHg or diastolic BP = 95 mmHg), 3 consecutive measures taken 5 minutes apart),
8. Severe or moderate hepatic impairment (Child – Pugh class C),
9. Active or symptomatic viral hepatitis or chronic liver disease (except Gilbert’s disease),
10. History of pituitary or adrenal dysfunction,
11. Clinically known significant heart disease in the past 6 months as
evidenced by myocardialinfarction, or arterial thrombotic events , severe
or unstable angina, or New York Heart association (NYHA) Class II-IV heart
disease or cardiac ejection fraction measurement of < 50% at baseline,
12. Atrial Fibrillation, or other cardiac arrhythmia requiring therapy,
13. Patients with unstable pulmonary disease (eg. Pulmonary embolism),
14. Pathological finding consistent with small cell carcinoma of the prostate,
15. History of 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 or docetaxel,
17. Administration of an investigational therapeutic within 30 days of randomization,
18. Patients already included in another therapeutic trial involving an experimental drug (patient in a non-experimental trial with no modification of the patient’s care can be included),
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.

Additional criteria for patients receiving docetaxel:
21. Patients with impaired vision should undergo a prompt and complete ophtalmologic examination. Patients with Cystoid Macular Oeadema cannot be included due to a potential risk of deterioration associated with docetaxel, the patient should not receive docetaxel.
22. Concomitant use of strong CYP3A4 inhibitors ( clarithromyin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin)


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

Health Condition(s) or Problem(s) studied

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

metastatic hormone-naïve prostate cancer
MedDRA version: 27.0 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

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

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

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

Secondary Objective: Castration resistance-free survival (CRFS)
• Serious Genitourinary event-free survival (S-GU-EFS)
• Prostate cancer specific survival
• Time to next skeletal-related event
• PSA response rate
• Prospective correlative study of PSA response/progression at 8
months after initiation of ADT
• Time to pain progression
• Time to chemotherapy for CRPC
• Quality of life
• Toxicity (with a specific focus on the use of long-term low-dose
steroids)
• Changes in bone mineral density (BMD)
• 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

Primary end point(s): The primary endpoints of this study are overall survival (OS) and
radiographic progression-free survival (rPFS).
Overall survival (OS) is defined as the time from randomization to the
time of death from any cause and radiographic progression-free survival
(rPFS) defined as the time from randomization to the radiographic
progression or death.
Radiographic progression is defined according to an adapted version of
Prostate Cancer Working Group 2 (PCWG2) criteria (either a RECISTprogression in case of measurable lesions or the appearance of at least 2
new lesions on bone scan). In contrast to PCWG2 criteria, a second bone
scan is not mandatory to confirm radiographic progression. The date of
radiographic progression will be the date of progression as per the above
definition.
It should be noted that a patient can enter the post-CRPC follow up if
progressive disease has been established by a PSA rise only, without
radiographic progressive disease. In this scenario, imaging monitoring
will continue every 6 months and radiographic progression may be
established later.

Secondary Outcome(s)

Secondary end point(s): •Castration resistance free survival (CRFS) is defined as the time from
randomization to the castrate-resistant (CRPC) status or death from any
cause.
CRPC is defined by cancer progression (either a confirmed PSA rise or a
radiographic 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 by a third measurement (measurement
Ang/mL.
A minimum delay of 2 weeks is recommended between measurements A
and B. A delay of 3 months is recommended between measurement B
and C. The date of progression will be the date of measurement C.
Serum testosterone should be obtained when PSA measurement C is
done.
In case of progression while serum testosterone is > 0.50 ng/mL, the
patient should be rapidly submitted to another method of castration
(chemical or surgical) and PSA + testosterone should be tested again to
confirm or not CRPC progression.
Radiographic progression is defined as per the above definition.
For patients alive without radiographic progression or confirmed PSA
rise at the time of analysis, data will be censored at the date of last
follow-up.
• Serious Genitourinary event-free survival (S-GU-EFS) is defined as
the time from randomization to the first occurrence of one of the
following events : urinary retention with need for a urinary catheter,
suprapubic catheter, double J stent, nephrostomy, treatment of the
prostate by radiotherapy (except that by randomization in arms C and D)
or trans-urethral resection of the prostate (TURP), prostatectomy or
death. It is assumed that prostate radiotherapy (and abiraterone) may
prevent or delay these serious genitourinary events. For patients alive
without Serious Genitourinary Event at the time of analysis, data will be
censored at the date of last follow-up.
• The prostate cancer-specific survival will be calculated from the date
of randomization to the date of the death due to prostate cancer. For
patients alive at the time of analysis, or who died from a cause other
than prostate cancer, data will be censored at the date of last follow-up,
• The time to next skeletal-related event will be defined by either a
fracture or a bone pain requiring radiation therapy or a spinal cord
compression or a preventive surgery to the bones. Events will be
evaluated by investigators. No systematic X-Ray will be perform
• PSA response rate will be assessed using a waterfall plot. Complete
PSA response is defined by an undetectable serum PSA level (<0.2
ng/mL).
• The prospective correlative study of PSA response/progression will
be evaluate at 8 months after initiation of ADT,
The time to pain progression will be evaluated by questionnaires
(BPI-SF) and calculated from the date of randomization to the first date
the patient experiences a BPI-SF increase by = 30% from baseline in the
BPI-SF worst pain intensity (items 3) observed at 2 consecutive
evaluations = 4 weeks apart.
• The time to chemotherapy will be calculated from the date of
randomization to the date of the first use of chemotherapy treatment for
CRPC
• Quality of life will be evaluated using the FACT-P and QLQ-C30
questionnaires.
• Toxicity (with a specific focus on the use of long-term low-dose
steroids) will be evaluated according to NCI-CTCAE v4.0
• Bone loss will be evaluated by bone mineral density (BMD) to
determine if patients receiving Abiraterone acetate and prednisone
and/or radiotherapy have an increase risk
• 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.

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

2012-000142-35-FR

UC-0160/1105

Source(s) of Monetary Support

JANSSEN-CILAG

Ethics review

Status: Approved
Approval date: 01/12/2014
Contact: