Prospective Phase III, randomized study evaluating the combination of hormonal treatment with or without docetaxel with or without radiotherapy with or without abiraterone and prednisone in patients with hormone-naïve metastatic prostate cancer.

Belgium, France, Germany, Ireland, Italy, Portugal, Romania, Spain, Switzerland (ICTRP)

ICTRP Trial ID
NCT01957436 (ICTRP)

Official title (approved by ethics committee)
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 (BASEC)

Academic title
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-Na?ve Prostate Cancer (ICTRP)

Public title
A Phase III Study for Patients With Metastatic Hormone-na?ve Prostate Cancer (ICTRP)

Disease under investigation
Metastatic Prostate Cancer (ICTRP)

Intervention under investigation
Drug: abiraterone acetate;Radiation: radiotherapy;Other: Androgen Deprivation Therapy;Drug: Docetaxel (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
Gender: Male
Maximum age: N/A
Minimum age: 18 Years
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/mm?

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.

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 metastases 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 5 mg
prednisone/prednisolone twice daily,

4. Active infection or other medical condition for which prednisone/prednisolone
(corticosteroid) use would be contra-indicated,

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 or B)

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
myocardial infarction, 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. Patient 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.

21. Patients with impaired vision should undergo a prompt and complete ophthalmologic
examination.

Patients with Cystoid Macular Oedema cannot be included due to a potential risk of
deterioration associated with docetaxel.

22. Concomitant use of strong CYP3A4 inhibitors (clarithromycin, indinavir, nefazodone,
nelfinavir, ritonavir, saquinavir, telithromycin.) (ICTRP)

not available

Primary and secondary end points
Survival;Survival (ICTRP)

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 initation of ADT;Time to pain progression;Time to chemotherapy for CRPC;Quality of life questionnaire - Core 30 (QLQ-C30);Functional Assessment of Cancer Therapy - Prostate (FACT-P);Toxicity (with a specific focus on the use of long-term low-dose steroids);Changes in bone mineral density;Correlation of biomarkers with outcome (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Janssen-Cilag Ltd.;European Organisation for Research and Treatment of Cancer - EORTC;Ipsen;Sanofi (ICTRP)

Additional contacts
Karim FIZAZI, Professor;Alberto BOSSI, Doctor, Gustave Roussy, Cancer Campus Grand Paris - Paris,Gustave Roussy, Cancer Campus Grand Paris - Paris (ICTRP)

Secondary trial IDs
UC-0160/1105 GETUG AFU-21 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT01957436 (ICTRP)