A Phase III Study for Patients With Metastatic Hormone-naïve Prostate Cancer

NCT ID: NCT01957436

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-11-13
• Study Completion Date: 2032-12-31

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.

Conditions

Metastatic Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

androgen deprivation therapy + docetaxel

Group Type: ACTIVE_COMPARATOR

Androgen Deprivation Therapy

Intervention Type: OTHER

The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Docetaxel

Intervention Type: DRUG

6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Arm B

androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone

Group Type: EXPERIMENTAL

abiraterone acetate

Intervention Type: DRUG

abiraterone 1000mg/day (4 tablets of 250 mg (PO) per day) + prednisone 5mg bid

Androgen Deprivation Therapy

Intervention Type: OTHER

The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Docetaxel

Intervention Type: DRUG

6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Arm C

Arm A + radiotherapy

Group Type: EXPERIMENTAL

radiotherapy

Intervention Type: RADIATION

74 Gy in 37 fractions 3D-Conformal RT or Intensity Modulated RT (IMRT)

Androgen Deprivation Therapy

Intervention Type: OTHER

The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Docetaxel

Intervention Type: DRUG

6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Arm D

Arm B + radiotherapy

Group Type: EXPERIMENTAL

abiraterone acetate

Intervention Type: DRUG

abiraterone 1000mg/day (4 tablets of 250 mg (PO) per day) + prednisone 5mg bid

radiotherapy

Intervention Type: RADIATION

74 Gy in 37 fractions 3D-Conformal RT or Intensity Modulated RT (IMRT)

Androgen Deprivation Therapy

Intervention Type: OTHER

The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Docetaxel

Intervention Type: DRUG

6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Interventions

abiraterone acetate

abiraterone 1000mg/day (4 tablets of 250 mg (PO) per day) + prednisone 5mg bid

Intervention Type: DRUG

radiotherapy

74 Gy in 37 fractions 3D-Conformal RT or Intensity Modulated RT (IMRT)

Intervention Type: RADIATION

Androgen Deprivation Therapy

The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Intervention Type: OTHER

Docetaxel

6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Intervention Type: DRUG

Other Intervention Names

Zytiga

Eligibility Criteria

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 :

Exclusion Criteria

• 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.

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.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Ipsen

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karim FIZAZI, Professor

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus Grand Paris - Paris

Alberto BOSSI, Doctor

Role: STUDY_CHAIR

Gustave Roussy, Cancer Campus Grand Paris - Paris

Locations

Onze Lieve Vrouw Ziekenhuis

Aalst, , Belgium

Hôpitaux Universitaires Bordet Erasme- Institut Jules Bordet

Brussels, , Belgium

Hopital de Jolimont

Haine-Saint-Paul, , Belgium

AZ Groeninge Kortrijk - Campus Vercruysselaan

Kortrijk, , Belgium

Cliniques Universitaires Saint-Luc

Leuven, , Belgium

U.Z. Leuven - Campus Gasthuisberg

Leuven, , Belgium

Clinique Claude Bernard

Albi, , France

Institut de cancerologie de l'Ouest

Angers, , France

Clinique Générale d'Annecy

Annecy, , France

Institut Sainte Catherine

Avignon, , France

Centre de la Baie

Avranches, , France

Centre d'Oncologie et de Radiothérapie du Pays Basque

Bayonne, , France

Chu Jean Minjoz

Besançon, , France

Centre Pierre Curie

Beuvry, , France

Institut Bergonie

Bordeaux, , France

Centre François Baclesse

Caen, , France

Centre Hospitalier Alpes Leman

Contamine-sur-Arve, , France

Chu de Mondor

Créteil, , France

Centre Leonard de Vinci

Dechy, , France

Centre Georges-François LECLERC

Dijon, , France

Clinique Sainte Marguerite

Hyères, , France

CHD Vendée

La Roche-sur-Yon, , France

Clinique Victor Hugo

Le Mans, , France

Chu de Limoges

Limoges, , France

Centre Léon Bérard

Lyon, , France

CHU Lyon Sud

Lyon, , France

Institut Paoli Calmettes

Marseille, , France

Chu Timone

Marseille, , France

Hôpital Nord

Marseille, , France

Centre Azuréen de Cancérologie

Mougins, , France

Centre Catherine de Sienne

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

CHU Carémeau

Nîmes, , France

CHR Orléans la source

Orléans, , France

Institut Curie

Paris, , France

Hôpital St Louis

Paris, , France

Hopital TENON

Paris, , France

Chic Quimper

Quimper, , France

Institut Jean Godinot

Reims, , France

Centre Eugène Marquis

Rennes, , France

Clinique Armoricaine de radiologie

Saint-Brieuc, , France

CHU ST ETIENNE - Hôpital Nord

Saint-Etienne, , France

CHP Saint Grégoire

Saint-Grégoire, , France

Institut de Cancérologie del'Ouest - site René Gauducheau

Saint-Herblain, , France

Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, , France

CENTRE DE CANCEROLOGIE Paris Nord

Sarcelles, , France

Strasbourg Oncologie Libérale

Strasbourg, , France

Hopitaux du Leman

Thonon-les-Bains, , France

Centre Hospitalier Intercommunal de Toulon - La Seyne sur Mer - Hôpital Sainte Musse

Toulon, , France

Institut Claudius Regaud

Toulouse, , France

Clinique Pasteur

Toulouse, , France

CHU de TOURS Hôpital Bretonneau

Tours, , France

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Centre d'Oncologie Saint Yves

Vannes, , France

INSTITUT GUSTAVE ROUSSY, Cancer Campus, Grand Paris

Villejuif, , France

Cork University Hospital

Cork, , Ireland

Adelaide and Meath incorporating National Children's hospital department

Dublin, , Ireland

Mater Misericordiae University Hospital

Dublin, , Ireland

Mater Private Hospital

Dublin, , Ireland

St Vincent's University Hospital

Dublin, , Ireland

Galway University Hospital

Galway, , Ireland

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

San Camillo Forlanini Hospitals

Roma, , Italy

Sc Radiotherapy Center Cluj SRL

Cluj-Napoca, , Romania

Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital De la Santa Creu I Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Vall d'Hebron University Hospital

Barcelona, , Spain

ICO Girona - Hospital Josep Trueta

Girona, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Althaia

Manresa, , Spain

'Hospital Clinico Virgen de la Victoria

Málaga, , Spain

'Parc Tauli Sabadell Hospital Universitari

Sabadell, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Institut Valenciano de Oncologia

Valencia, , Spain

Fondation Dr. Henri Dubois-Ferrière Dinu Lipatti

Geneva, , Switzerland

Centre Hospitalier Universitaire Vaudois

Lausanne, , Switzerland

Countries

Belgium; France; Ireland; Italy; Romania; Spain; Switzerland

References

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Reference Type: DERIVED

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Reference Type: DERIVED

PMID: 39923274 (View on PubMed)

Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Flechon A, Tombal B, Supiot S, Berthold D, Ronchin P, Kacso G, Gravis G, Calabro F, Berdah JF, Hasbini A, Silva M, Thiery-Vuillemin A, Latorzeff I, Mourey L, Laguerre B, Abadie-Lacourtoisie S, Martin E, El Kouri C, Escande A, Rosello A, Magne N, Schlurmann F, Priou F, Chand-Fouche ME, Freixa SV, Jamaluddin M, Rieger I, Bossi A; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707. doi: 10.1016/S0140-6736(22)00367-1. Epub 2022 Apr 8.

Reference Type: DERIVED

PMID: 35405085 (View on PubMed)

Other Identifiers

UC-0160/1105 GETUG AFU-21

Identifier Type: -

Identifier Source: org_study_id