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

Metastatic Prostate Cancer Clinical Trial

— PEACE1  

Official 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-Naïve Prostate Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01957436
• Other study ID #: UC-0160/1105 GETUG AFU-21
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 13, 2013
• Est. completion date: December 2032

Study information

• Verified date: November 2023
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1173
• Est. completion date: December 2032
• Est. primary completion date: August 18, 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 :

• 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.)

Related Conditions & MeSH terms

• Metastatic Prostate Cancer
• Prostatic Neoplasms

Intervention

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

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

Other:
• Androgen Deprivation Therapy
The ADT must consist in either LHRH agonist, LHRH antagonist or orchiectomy

Drug:
• Docetaxel
6 cycles at 75mg/m²/cycle, one cycle every 3 weeks

Locations

Country	Name	City	State
Belgium	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	U.Z. Leuven - Campus Gasthuisberg	Leuven
Belgium	Cliniques Universitaires Saint-Luc	Louvain
France	Clinique Claude Bernard	Albi
France	Institut de cancerologie de l'Ouest	ANGERS Cedex 9
France	Clinique Générale d'Annecy	Annecy
France	Institut Sainte Catherine	Avignon Cedex 9
France	Centre de la Baie	Avranches
France	Centre d'Oncologie et de Radiothérapie du Pays Basque	Bayonne
France	Chu Jean Minjoz	Besancon
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	Creteil
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	CHU Lyon Sud	Lyon
France	Centre Léon Bérard	Lyon cedex 08
France	Hôpital Nord	Marseille
France	Institut Paoli Calmettes	Marseille
France	Chu Timone	MARSEILLE Cedex 5
France	Centre Azuréen de Cancérologie	Mougins
France	Centre Catherine de Sienne	Nantes Cedex 2
France	Centre Antoine Lacassagne	Nice
France	CHU Carémeau	NIMES Cedex 9
France	CHR Orléans la source	Orleans
France	Hôpital St Louis	Paris
France	Hopital TENON	Paris
France	Institut Curie	Paris
France	Chic Quimper	Quimper
France	Institut Jean Godinot	Reims
France	Centre Eugène Marquis	RENNES Cedex
France	Clinique Armoricaine de radiologie	Saint Brieuc
France	CHU ST ETIENNE - Hôpital Nord	Saint Etienne
France	CHP Saint Grégoire	Saint Gregoire
France	Institut de Cancérologie del'Ouest - site René Gauducheau	Saint-herblain
France	CENTRE DE CANCEROLOGIE Paris Nord	Sarcelles
France	Institut de Cancérologie Lucien Neuwirth	St PRIEST EN JAREZ
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 Cedex
France	Clinique Pasteur	TOULOUSE Cedex 3
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
Ireland	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
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	San Camillo Forlanini Hospitals	Roma
Romania	Sc Radiotherapy Center Cluj SRL	Cluj
Spain	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	'Hospital Clinico Virgen de la Victoria	Málaga
Spain	Althaia	Manresa
Spain	'Parc Tauli Sabadell Hospital Universitari	Sabadell
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Institut Valenciano de Oncologia	Valencia
Switzerland	Fondation Dr. Henri Dubois-Ferrière Dinu Lipatti	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne

Sponsors (5)

Lead Sponsor	Collaborator
UNICANCER	European Organisation for Research and Treatment of Cancer - EORTC, Ipsen, Janssen-Cilag Ltd., Sanofi

Countries where clinical trial is conducted

Belgium,  France,  Ireland,  Italy,  Romania,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	Overall and radiographic progression-free survival in patients with metastatic hormone-naïve prostate cancer treated by androgen deprivation therapy and docetaxel	7.5 years after the first inclusion
Primary	Survival	Overall and radiographic progression-free survival in hormone-naïve prostate cancer patients with low metastatic burden whatever the standard of care received	9.5 years after the first inclusion
Secondary	Castration resistance-free survival (CRFS)		9.5 years after the first inclusion
Secondary	Serious Genitourinary event-free survival (S-GU-EFS)		9.5 years after the first inclusion
Secondary	Prostate cancer specific survival		9.5 years after the first inclusion
Secondary	Time to next skeletal-related event		9.5 years after the first inclusion
Secondary	PSA response rate		9.5 years after the first inclusion
Secondary	Prospective correlative study of PSA response/progression at 8 months after initation of ADT		9.5 years after the first inclusion
Secondary	Time to pain progression	will be evaluated by questionnaires	9.5 years after the first inclusion
Secondary	Time to chemotherapy for CRPC		9.5 years after the first inclusion
Secondary	Quality of life questionnaire - Core 30 (QLQ-C30)	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.; The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.; All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At baseline, 6 months, 18 months, and at the end of treatment (up to 9.5 years)
Secondary	Functional Assessment of Cancer Therapy - Prostate (FACT-P)	The FACT-P is a self-assessment questionnaire to estimate the health-related quality of life in men with prostate cancer. This questionnaire, composed of 39 items consists of four subscales: Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), Functional Well-Being (7 items), and prostate cancer subscale (12 items). Subscales are rated on 5-point Likert-type scale (from 0 = "Not at all" to 4 = "Very much"). For all subscales, a higher score represents better quality of life.	At baseline, 6 months, 12 months, 18 months, and at the end of treatment (up to 9.5 years)
Secondary	Toxicity (with a specific focus on the use of long-term low-dose steroids)	The National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.	Throughout study completion, up to 9.5 years
Secondary	Changes in bone mineral density	X-rays are used to measure how many grams of calcium and other bone minerals are packed into a segment of bone	At baseline, 6 months, 12 months, and 24 months
Secondary	Correlation of biomarkers with outcome	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.	9.5 years after the first inclusion