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

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ClinicalTrials.gov Identifier: NCT01952223
Recruitment Status : Recruiting
First Posted : September 27, 2013
Last Update Posted : May 17, 2018
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
UNICANCER

Tracking Information
First Submitted Date  ICMJE September 24, 2013
First Posted Date  ICMJE September 27, 2013
Last Update Posted Date May 17, 2018
Actual Study Start Date  ICMJE December 2013
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
progression free survival [ Time Frame: 10 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01952223 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2013)
  • prostate-specific antigen response at 3 months [ Time Frame: 10 years ]
  • biochemical progression-free survival [ Time Frame: 10 years ]
  • metastases-free survival [ Time Frame: 10 years ]
  • local relapse-free survival [ Time Frame: 10 years ]
  • overall survival [ Time Frame: 10 years ]
  • prostate cancer-specific survival [ Time Frame: 10 years ]
  • acute toxicity [ Time Frame: 10 years ]
  • impact of treatment on serum testosterone [ Time Frame: 10 years ]
  • long-term toxicity [ Time Frame: 10 years ]
  • predictive biomarkers of treatment efficacy [ Time Frame: 10 years ]
  • quality of life [ Time Frame: 10 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase III of Cabazitaxel and Pelvic Radiotherapy in Localized Prostate Cancer and High-risk Features of Relapse
Official Title  ICMJE A Randomized Phase III, Factorial Design, of Cabazitaxel and Pelvic Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse
Brief Summary The objective of this study is to assess the effect of neoadjuvant cabazitaxel and pelvic radiotherapy in combination with 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.
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 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 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  ICMJE Interventional
Study Phase Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Adenocarcinoma of Prostate
  • Progression of Prostate Cancer
Intervention  ICMJE
  • Drug: Cabazitaxel
    Cabazitaxel administered at 25mg/m2 as a 1 hour intravenous infusion every 3 weeks (1 cycle = 21 days) for 4 cycles
    Other Name: jevtana
  • 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
  • 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
Study Arms
  • Experimental: ADT + pelvic RT

    ADT for a total duration of 3 years i.e.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
    Intervention: Radiation: Pelvic radiotherapy
  • 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
    Interventions:
    • Drug: Cabazitaxel
    • Radiation: prostate radiotherapy
  • 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
    Interventions:
    • Drug: Cabazitaxel
    • Radiation: Pelvic radiotherapy
  • 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
    Intervention: Radiation: prostate radiotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2013)
1048
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date December 2032
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) 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 ULN; AST and ALT ≤ 2.5 x ULN 13) Renal function (creatinine clearance using the CKD-EPI formula (Chronic Kidney Disease Epidemiology group) ≥ 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, 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 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

Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Muriel HABIBIAN +33(0)176647807 m-habibian@unicancer.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01952223
Other Study ID Numbers  ICMJE GETUG-AFU 23 - UC-0160/1202
2012-000566-38 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party UNICANCER
Study Sponsor  ICMJE UNICANCER
Collaborators  ICMJE Sanofi
Investigators  ICMJE
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 VENDEE - La Roche sur Yon
Principal Investigator: Aude FLECHON, Doctor CENTRE LEON BERARD - 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 Cancérologie 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 Centre Hospitalier Privé Saint-Grégoire
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 Hôpital 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 Hôpital 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 Hospital Universitario de Salamanca
Principal Investigator: Salvador VILLA i FREIXA, Doctor ICO Badalona - H.U. Germans Trias
Principal Investigator: Daniel CASTELLANO, Doctor Hospital Universitario 12 de Octubre
PRS Account UNICANCER
Verification Date May 2018

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