A Phase III of Cabazitaxel and Pelvic Radiotherapy in Localized Prostate Cancer and High-risk Features of Relapse (PEACE2)

A Randomized Phase III, Factorial Design, of Cabazitaxel and Pelvic Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse

The objective of this study is to assess the effect of neoadjuvant cabazitaxel and pelvic radiotherapy in combination with androgen deprivation therapy (ADT)-radiotherapy on clinical progression-free survival in patients with high-risk localized prostate cancer (with a stringent selection of patients with at least 2 high-risk features), in a 2 by 2 factorial trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Adenocarcinoma of Prostate; Progression of Prostate Cancer
• Intervention / Treatment: Radiation: Pelvic radiotherapy; Drug: Cabazitaxel; Radiation: prostate radiotherapy

Detailed Description

Eligible patients can be randomized via the TENALEA web site process that insure centralization of the randomization.

Randomization will be performed according a 1:1:1:1 ratio. The randomization will be stratified (by minimization) according to the number of risk factors (2 vs.3), disease extent (pN- vs. pN+ vs. pNx) and the site.

The minimization will be defined with a similar weight for all 3 stratification factors and a probability of assigning the treatment that minimize the imbalance equal to 80%.

The main analysis of progression-free survival (PFS) will be event driven (> 247 events). It will likely be performed when the median follow-up is approximately 6 years, i.e. 4 years after the inclusion of the last patient (assuming an accrual of 4 years).

A long-term analysis (allowing for robust PFS and overall survival (OS) data) will also be performed when the follow-up is approximately 10 years. Its exact timing will be discussed with the steering committee and the IDMC.

An interim analysis of the primary endpoint is planned. This interim analysis will be performed at a 0.001 level (Peto) after 50% of the events i.e. 125 have occurred.

For each comparison (CT comparison and pelvic RT comparison) the two PFS curves will be compared using the adjusted logrank test (bilateral test): adjusted logrank on pelvic RT for the CT comparison and on CT for the pelvic RT comparison. A multivariate analysis using the Cox model will also be used.

An Independent Data Monitoring Committee (IDMC) composed of international experts (at least 2 physicians and 1 statistician) will be selected.

For safety purpose, the IDMC will meet after the inclusion of 20 patients (and then again after accrual of 50 patients) in the cabazitaxel and pelvic radiotherapy arm, to assess tolerance, (i.e. after the inclusion of approximately 80 and then 200 patients in the trial). Depending on the results of this feasibility phase and of any new relevant clinical results in such a population, the remaining patients (n=848) will be enrolled.

During this second phase, the IDMC will then meet every two years approximately during accrual to carefully assess accrual rate and toxicity and examine the efficacy interim analysis results in the light of the results of similar trials.

• Study Type: Interventional
• Enrollment (Actual): 761
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Villejuif, France, F-94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Any T histologically confirmed adenocarcinoma of the prostate
2. No clinically or radiologically suspected metastases, including no enlarged pelvic lymph nodes (> 1 cm in small diameter)
3. Gleason score ≥ 6

4. Meets at least 2 of the following criteria for high-risk:

   • Gleason score ≥ 8
   • T3 or T4 disease (T3 defined by MRI is acceptable)
   • Prostate-specific antigen equal or greater than 20 ng/mL
5. No prior treatment for prostate cancer except lymph node dissection (patients with pN- and pN+ disease can be accrued) or ADT (started up to 6 weeks before randomization).
6. 18 years ≤ Age ≤ 75 years
7. Eastern Cooperative Oncology Group (ECOG) 0-1 performance status
8. Expected life expectancy of more than 10 years
9. Absolute neutrophil count ≥ 1.5 x 10⁹/L
10. Platelets ≥ 100 x 10⁹/L
11. Hb ≥ 9.0 g/dL
12. Hepatic function: serum bilirubin ≤ 1 upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
13. Renal function (creatinine clearance using the Chronic Kidney Disease Epidemiology group (CKD-EPI) formula ≥ 60 mL/min).
14. Potentially reproductive patients must agree to use an effective contraceptive method while on treatment and for 6 months after the final dose of investigational product.
15. Patients must be affiliated to a Social Security System or should fulfill the country legislation for clinical trials.
16. Patients who have received the information sheet and signed the informed consent form.
17. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures

Exclusion Criteria:

1. Patients with other known concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as:

   1. infection,
   2. cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, left ventricular ejection fraction (LVEF) > grade 2,
   3. uncontrolled diabetes mellitus,
   4. current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, stable chronic liver disease per investigator assessment),
   5. renal disease,
   6. active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded,
   7. known severely impaired lung function (spirometry and diffusing capacity of the lungs for carbon monoxide (DLCO) 70% or less of normal and O2 saturation of 88% or less at rest on room air).
2. Other prior malignancy within the last 5 years, except basal cell skin cancer
3. Physical or psychological condition that would preclude study compliance
4. Hypersensitivity to cabazitaxel (hypersensitivity reaction ≥grade 3), to other taxanes, or to any excipients of the formulation including polysorbate 80
5. 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; those conditions should be discussed with the patient before registration in the trial.
6. Patients who received any other investigational drugs within the 30 days prior to the start of cabazitaxel.
7. Previous pelvic irradiation that make prostatic irradiation impossible
8. Severe GI disorders precluding pelvic irradiation
9. Patients already included in another therapeutic trial involving an experimental drug
10. Individual deprived of liberty or placed under the authority of a tutor.
11. Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (see Appendix 6). A one week wash-out period is necessary for patients who are already on these treatments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ADT + pelvic RT; ADT for a total duration of 3 years i.e. luteinizing hormone-releasing hormone (LHRH) agonist or LHRH antagonist +/-Peripheral anti-androgen Pelvic RT (by IMRT or IGRT protocol): Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy	Radiation: Pelvic radiotherapy; Prostate+pelvic RT (2 Gy fractions, 5 times per week): Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
Experimental: ADT + Cabazitaxel + prostate RT; ADT Cabazitaxel: 4 CT cycles Prostate-only RT (IMRT or IGRT): Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy	Drug: Cabazitaxel; Cabazitaxel administered at 25 mg/m² as a 1 hour intravenous infusion every 3 weeks (1 cycle = 21 days) for 4 cycles; Other Names: jevtana; Radiation: prostate radiotherapy; Prostate-only RT (2 Gy fractions, 5 times per week): Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy
Experimental: ADT + cabazitaxel + pelvic RT; ADT Cabazitaxel: 4 CT cycles Pelvic RT (IMRT or IGRT): Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy	Radiation: Pelvic radiotherapy; Prostate+pelvic RT (2 Gy fractions, 5 times per week): Phase 1: pelvic radiotherapy (prostate, seminal vesicles, ilio-obturator, presacral lymph nodes) (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy; Drug: Cabazitaxel; Cabazitaxel administered at 25 mg/m² as a 1 hour intravenous infusion every 3 weeks (1 cycle = 21 days) for 4 cycles; Other Names: jevtana
Active Comparator: ADT + prostate radiotherapy; ADT for a total duration of 3 years: LHRH agonist or LHRH antagonist +/- anti-androgen Prostate-only RT (IMRt or IGRT): Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy	Radiation: prostate radiotherapy; Prostate-only RT (2 Gy fractions, 5 times per week): Phase 1: prostate + seminal vesicle radiotherapy (46 or 50 Gy according to the center); Phase 2: prostate-only boost (EBRT) up to 74-78 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
progression free survival	10 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	10 years
prostate-specific antigen response at 3 months	10 years
biochemical progression-free survival	10 years
metastases-free survival	10 years
local relapse-free survival	10 years
prostate cancer-specific survival	10 years
acute toxicity	10 years
impact of treatment on serum testosterone	10 years
long-term toxicity	10 years
predictive biomarkers of treatment efficacy	10 years
quality of life	10 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Collaborators: Sanofi
• Investigators: Principal Investigator: Emmanuelle BOMPAS, Doctor, ICO-René Gauducheau - St Herblain; Principal Investigator: Jean-Christophe EYMARD, Doctor, Institut Jean Godinot - Reims; Principal Investigator: Guilhem ROUBAUD, Doctor, Institut Bergonié Bordeaux; Principal Investigator: Philippe BEUZEBOC, Doctor, Institut Curie Paris; Principal Investigator: Aline GUILLOT, Doctor, Institut de Cancérologie Lucien Neuwirth -ST Priest en Jarez; Principal Investigator: Claude EL KOURI, Doctor, Centre Catherine de Sienne - Nantes; Principal Investigator: Frank PRIOU, Doctor, CHD Vendée - La Roche sur Yon; Principal Investigator: Aude FLECHON, Doctor, Centre Léon Bérard - Lyon; Principal Investigator: Igor LATORZEFF, Doctor, Clinique Pasteur Toulouse; Principal Investigator: Karim FIZAZI, Professor, Gustave Roussy, Cancer Campus Grand Paris-Paris; Principal Investigator: Jean BERDAH, Doctor, Clinique Ste Marguerite - Hyères; Principal Investigator: Stéphane CULINE, Professor, Hôpital St Louis - Paris; Principal Investigator: Sophie ABADIE-LACOURTOISIE, Doctor, ICO - Paul Papin - Angers; Principal Investigator: Philippe FOURNERET, Doctor, Centre hospitalier de Chambéry - Chambéry; Principal Investigator: Alain GRANDGIRARD, Doctor, Centre hospitalier de Mulhouse - mulhouse; Principal Investigator: Dominique BESSON, Doctor, Clinique Armoricaine de Radiologie - St Brieuc; Principal Investigator: Loïc MOUREY, Doctor, Institut Claudius REGAUD - Toulouse; Principal Investigator: Alain RUFFION, Professor, Centre hospitalier Lyon Sud - Pierre Bénite; Principal Investigator: Tristan MAURINA, Doctor, CHRU Jean Minoz - Besançon; Principal Investigator: Pierre CLAVERE, Professor, CHU Limoges - Limoges; Principal Investigator: Véronique BECKENDORF, Doctor, Institut de Cancerologie de Lorraine; Principal Investigator: Joan Carles, Doctor, Hospital Vall d'Hebron - Barcelone; Principal Investigator: Riccardo Valdagni, Professor, Fondazione IRCCS Istituto Nazionale dei tumori - Milan; Principal Investigator: Philippe RONCHIN, Docteur, Centre Azuréen de Cancérologie - Mougins; Principal Investigator: Eric LECHEVALLIER, Professor, Hôpital de la conception - Marseille; Principal Investigator: Gwenaëlle GRAVIS, Doctor, Institut Paoli Calmettes - Marseille; Principal Investigator: Elise CHAMPEAUX-ORANGE, Doctor, CHR Orléans La Source - Orléans; Principal Investigator: Xavier ARTIGNAN, Doctor, Saint-Gregoire Private Hospital Center; Principal Investigator: Anne DONEUX, Doctor, Clinique Générale d'Annecy; Principal Investigator: Thibaud HAASER, Doctor, Hôpital Haut L'Evèque - Pessac; Principal Investigator: Youssef TAZI, Doctor, STRASBOURG ONCOLOGIE LIBERALE - CLINIQUE SAINTE ANNE - Strasbourg; Principal Investigator: Stéphane OUDARD, Professor, HOPITAL EUROPEEN GEORGES POMPIDOU - Paris; Principal Investigator: Brigitte LAGUERRE, Doctor, CENTRE EUGENE MARQUIS - Rennes; Principal Investigator: Hakim MAHAMMEDI, Doctor, CENTRE JEAN PERRIN - Clermont Ferrand; Principal Investigator: Nadine HOUEDE, Doctor, CHRU de Nîmes Caremeau - Nîmes; Principal Investigator: Gaël DEPLANQUE, Doctor, CH Paris Saint Joseph - Paris; Principal Investigator: Marjorie BACIUCHKA-PALMARO, Doctor, Hopital Nord Marseille; Principal Investigator: yazid BELKACEMI, Doctor, Hôpital Henri Mondor - Créteil; Principal Investigator: Mostefa BENNAMOUN, Doctor, L'Institut Mutualiste Montsouris-Paris; Principal Investigator: ali HASBINI, Doctor, Clinique Pasteur - Brest; Principal Investigator: Emmanuel GROSS, Doctor, Hôpital privé Clairval - Marseille; Principal Investigator: Bérengère NARCISO RAHARIMANANA, Doctor, CHU de Tours Hopital Bretonneau; Principal Investigator: Carole HELISSEY, Doctor, Hôpital d'instruction des armées Bégin - St mandé; Principal Investigator: Marta GUIX, Doctor, Hospital Del Mar; Principal Investigator: Begoña PEREZ-VALDERRAMA, Doctor, Hospital Universitario Virgen del Rocio -Sevilla; Principal Investigator: Enrique GALLARDO, Doctor, Parc Tauli Sabadell Hospital Universitari - Sabadell; Principal Investigator: Maria SAEZ, Doctor, H. Virgen de la Victoria - Malaga; Principal Investigator: Montserrat DOMENECH, Doctor, Althaia, Xarxa Universitaria i assistencial de Manresa; Principal Investigator: Sergio VAZQUEZ ESTEVEZ, Doctor, H. Lucus Augusti - Lugo; Principal Investigator: Luis Miguel Anton APARICIO, Doctor, H. Teresa Herrera - Coruna; Principal Investigator: Maria José MENDEZ VIDAL, Doctor, H. Reina Sofia; Principal Investigator: Pilar LOPEZ CRIADO, Doctor, M.D. Anderson Cancer Center; Principal Investigator: Begoña MELLADO GONZALEZ, Doctor, Hospital Clinic of Barcelona; Principal Investigator: Francisco GOMEZ VEIGA, Doctor, University of Salamanca; Principal Investigator: Salvador VILLA i FREIXA, Doctor, ICO Badalona - H.U. Germans Trias; Principal Investigator: Daniel CASTELLANO, Doctor, Hospital Universitario 12 de Octubre

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2013
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2041

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: September 24, 2013
• First Posted (Estimated): September 27, 2013

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: relapse; Radiotherapy; adenocarcinoma; Androgen Deprivation Therapy; prostate; Cabazitaxel
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Recurrence; Adenocarcinoma
• Other Study ID Numbers: GETUG-AFU 23 - UC-0160/1202; 2012-000566-38 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No