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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by UNICANCER
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01952223
First received: September 24, 2013
Last updated: January 6, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of Prostate
Progression of Prostate Cancer
Drug: Cabazitaxel
Radiation: Pelvic radiotherapy
Radiation: prostate radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III, Factorial Design, of Cabazitaxel and Pelvic Radiotherapy in Patients With Localized Prostate Cancer and High-risk Features of Relapse

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • progression free survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • prostate-specific antigen response at 3 months [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • biochemical progression-free survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • metastases-free survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • local relapse-free survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • prostate cancer-specific survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • acute toxicity [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  • impact of treatment on serum testosterone [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • long-term toxicity [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]
  • predictive biomarkers of treatment efficacy [ Time Frame: 10 years ] [ Designated as safety issue: No ]
  • quality of life [ Time Frame: 10 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 1048
Study Start Date: September 2013
Estimated Study Completion Date: September 2026
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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 25mg/m2 as a 1 hour intravenous infusion every 3 weeks (1 cycle = 21 days) for 4 cycles
Other Name: 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
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
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 ≥7 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).

    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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01952223

Contacts
Contact: Muriel HABIBIAN +33(0)176647807 m-habibian@unicancer.fr

Locations
France
Institut Gustave Roussy Recruiting
Villejuif, France, F-94805
Contact: Karim Fizazi, MD, PhD    33-1-4211-6264    fizazi@igr.fr   
Sponsors and Collaborators
UNICANCER
Investigators
Principal Investigator: Emmanuelle BOMPAS, Doctor ICO-René Gauducheau - St Herblain
Principal Investigator: Tan Dat NGUYEN, Professor Institut Jean Godinot - Reims
Principal Investigator: Guilhem ROUBAUD, Doctor Institut Bergonié - Bordeaux
Principal Investigator: Jean-Marc FERRERO, Professor Centre Antoine Lacassagne - Nice
Principal Investigator: Jean-michel VANNETZEL, Doctor Clinique Hartmann - neuilly sur Seine
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: Patricia BURBAN-PROVOST, 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: Antoine THIERY-VUILLEMIN, Doctor CHRU Jean Minoz - Besançon
Principal Investigator: Pierre CLAVERE, Professor CHU Limoges - Limoges
Principal Investigator: Véronique BECKENDORF, Doctor Institut de cancérologie de Lorraine, Vandoeuvre les Nancy
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01952223     History of Changes
Other Study ID Numbers: UC-0160/1202, 2012-000566-38
Study First Received: September 24, 2013
Last Updated: January 6, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Italy: The Italian Medicines Agency

Keywords provided by UNICANCER:
adenocarcinome
prostate
relapse
Radiotherapy
Androgen Deprivation Therapy
Cabazitaxel

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014