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

Phase 3

Active, not recruiting

• Conditions: Metastatic Prostate Cancer
• Interventions: Radiation: radiotherapy; Drug: abiraterone acetate; Other: Androgen Deprivation Therapy; Drug: Docetaxel

• Registration Number: NCT01957436
• Lead Sponsor: UNICANCER

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.

Study Timeline

• Study First Submitted: 2013-09-24
• Study First Submitted QC: 2013-09-30
• Study First Posted: 2013-10-08
• Study Start: 2013-11-13
• Primary Completion: 2021-08-18
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-11
• Study Completion: 2032-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 1173

Inclusion Criteria

Not provided

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.)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm C	Androgen Deprivation Therapy	Arm A + radiotherapy
Arm D	Androgen Deprivation Therapy	Arm B + radiotherapy
Arm A	Androgen Deprivation Therapy	androgen deprivation therapy + docetaxel
Arm B	Androgen Deprivation Therapy	androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Arm B	Docetaxel	androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Arm C	radiotherapy	Arm A + radiotherapy
Arm B	abiraterone acetate	androgen deprivation therapy + docetaxel + abiraterone acetate + prednisone
Arm D	radiotherapy	Arm B + radiotherapy
Arm A	Docetaxel	androgen deprivation therapy + docetaxel
Arm C	Docetaxel	Arm A + radiotherapy
Arm D	abiraterone acetate	Arm B + radiotherapy
Arm D	Docetaxel	Arm B + radiotherapy

Primary Outcome Measures

Name	Time	Method
Survival	9.5 years after the first inclusion	Overall and radiographic progression-free survival in hormone-naïve prostate cancer patients with low metastatic burden whatever the standard of care received

Secondary Outcome Measures

Name	Time	Method
Time to chemotherapy for CRPC	9.5 years after the first inclusion
Castration resistance-free survival (CRFS)	9.5 years after the first inclusion
Serious Genitourinary event-free survival (S-GU-EFS)	9.5 years after the first inclusion
Prostate cancer specific survival	9.5 years after the first inclusion
Quality of life questionnaire - Core 30 (QLQ-C30)	At baseline, 6 months, 18 months, and at the end of treatment (up to 9.5 years)	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.
Toxicity (with a specific focus on the use of long-term low-dose steroids)	Throughout study completion, up to 9.5 years	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.
Time to next skeletal-related event	9.5 years after the first inclusion
Time to pain progression	9.5 years after the first inclusion	will be evaluated by questionnaires
Correlation of biomarkers with outcome	9.5 years after the first inclusion	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.
Prospective correlative study of PSA response/progression at 8 months after initation of ADT	9.5 years after the first inclusion
Changes in bone mineral density	At baseline, 6 months, 12 months, and 24 months	X-rays are used to measure how many grams of calcium and other bone minerals are packed into a segment of bone
Functional Assessment of Cancer Therapy - Prostate (FACT-P)	At baseline, 6 months, 12 months, 18 months, and at the end of treatment (up to 9.5 years)	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.
PSA response rate	9.5 years after the first inclusion

Trial Locations

Locations (77)

Hospital Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Vall d'Hebron University Hospital; 🇪🇸 Barcelona, Spain

ICO Girona - Hospital Josep Trueta; 🇪🇸 Girona, Spain

Hospital De la Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Althaia; 🇪🇸 Manresa, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Institut Valenciano de Oncologia; 🇪🇸 Valencia, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

'Hospital Clinico Virgen de la Victoria; 🇪🇸 Málaga, Spain

'Parc Tauli Sabadell Hospital Universitari; 🇪🇸 Sabadell, Spain

Centre d'Oncologie et de Radiothérapie du Pays Basque; 🇫🇷 Bayonne, France

Institut Curie; 🇫🇷 Paris, France

Institut de Cancérologie Lucien Neuwirth; 🇫🇷 St PRIEST EN JAREZ, France

Institut de Cancérologie del'Ouest - site René Gauducheau; 🇫🇷 Saint-herblain, France

Hôpital St Louis; 🇫🇷 Paris, France

Cliniques Universitaires Saint-Luc; 🇧🇪 Louvain, Belgium

Clinique Claude Bernard; 🇫🇷 Albi, France

Institut Sainte Catherine; 🇫🇷 Avignon Cedex 9, France

Centre de la Baie; 🇫🇷 Avranches, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre François Baclesse; 🇫🇷 Caen, France

Chu de Mondor; 🇫🇷 Creteil, France

CHD Vendée; 🇫🇷 La ROCHE sur YON, France

Hôpitaux Universitaires Bordet Erasme- Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Centre Leonard de Vinci; 🇫🇷 Dechy, France

Centre Léon Bérard; 🇫🇷 Lyon cedex 08, France

Institut Paoli Calmettes; 🇫🇷 Marseille, France

CHU Carémeau; 🇫🇷 NIMES Cedex 9, France

CHP Saint Grégoire; 🇫🇷 Saint Gregoire, France

CENTRE DE CANCEROLOGIE Paris Nord; 🇫🇷 Sarcelles, France

Hopitaux du Leman; 🇫🇷 Thonon-les-bains, France

CHU de TOURS Hôpital Bretonneau; 🇫🇷 Tours, France

St Vincent's University Hospital; 🇮🇪 Dublin, Ireland

Onze Lieve Vrouw Ziekenhuis; 🇧🇪 Aalst, Belgium

AZ Groeninge Kortrijk - Campus Vercruysselaan; 🇧🇪 Kortrijk, Belgium

Chu Jean Minjoz; 🇫🇷 Besancon, France

Centre Georges-François LECLERC; 🇫🇷 Dijon, France

Centre Catherine de Sienne; 🇫🇷 Nantes Cedex 2, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CHU Lyon Sud; 🇫🇷 Lyon, France

Hopital de Jolimont; 🇧🇪 Haine Saint Paul, Belgium

Clinique Générale d'Annecy; 🇫🇷 Annecy, France

Centre Pierre Curie; 🇫🇷 Beuvry, France

Clinique Sainte Marguerite; 🇫🇷 Hyères, France

Chu de Limoges; 🇫🇷 Limoges, France

Chu Timone; 🇫🇷 MARSEILLE Cedex 5, France

CHR Orléans la source; 🇫🇷 Orleans, 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

Strasbourg Oncologie Libérale; 🇫🇷 Strasbourg, France

Centre Hospitalier Intercommunal de Toulon - La Seyne sur Mer - Hôpital Sainte Musse; 🇫🇷 Toulon, France

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

U.Z. Leuven - Campus Gasthuisberg; 🇧🇪 Leuven, Belgium

Institut de cancerologie de l'Ouest; 🇫🇷 ANGERS Cedex 9, France

Centre Hospitalier Alpes Leman; 🇫🇷 Contamine Sur Arve, France

Clinique Victor Hugo; 🇫🇷 Le Mans, France

Hôpital Nord; 🇫🇷 Marseille, France

Centre Azuréen de Cancérologie; 🇫🇷 Mougins, France

Hopital TENON; 🇫🇷 Paris, France

Chic Quimper; 🇫🇷 Quimper, France

Institut Claudius Regaud; 🇫🇷 TOULOUSE Cedex, France

Centre d'Oncologie Saint Yves; 🇫🇷 Vannes, France

Galway University Hospital; 🇮🇪 Galway, Ireland

INSTITUT GUSTAVE ROUSSY, Cancer Campus, Grand Paris; 🇫🇷 Villejuif, France

Adelaide and Meath incorporating National Children's hospital department; 🇮🇪 Dublin, Ireland

Sc Radiotherapy Center Cluj SRL; 🇷🇴 Cluj, Romania

Fondation Dr. Henri Dubois-Ferrière Dinu Lipatti; 🇨🇭 Geneva, Switzerland

Clinique Pasteur; 🇫🇷 TOULOUSE Cedex 3, France

Institut de Cancérologie de Lorraine; 🇫🇷 Vandœuvre-lès-Nancy, France

Cork University Hospital; 🇮🇪 Cork, Ireland

Mater Private Hospital; 🇮🇪 Dublin, Ireland

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori; 🇮🇹 Meldola, Italy

San Camillo Forlanini Hospitals; 🇮🇹 Roma, Italy

Centre Hospitalier Universitaire Vaudois; 🇨🇭 Lausanne, Switzerland