A Study of Immediate 9 Months Adjuvant Hormone Therapy With Triptorelin 11.25 mg Versus Active Surveillance After Radical Prostatectomy in High Risk Prostate Cancer Patients.
- Registration Number
- NCT01753297
- Lead Sponsor
- Ipsen
- Brief Summary
The purpose of this study is to assess the benefit of immediate hormonal treatment after Radical Prostatectomy in Chinese and Russian patients with high risk prostate cancer. To reach this target, the trial will compare a group of patients treated with triptorelin at 8 weeks after the surgery and for a duration of 9 months (3 injections) versus another group (called "active surveillance group") who will be not receiving triptorelin. Both groups will be followed every 3 months to monitor any sign of disease progression during a minimum of 36 months
- Detailed Description
This trial is a phase IV (in Russia and China) as approved indication is locally advanced or metastatic prostate cancer in both countries.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 226
- Histopathologically confirmed adenocarcinoma of the prostate
- Radical Prostatectomy with curative intent performed no more than 8 weeks before randomisation
- High risk criteria of disease progression, defined as follows:
Gleason score ≥8 on prostatectomy specimen, and/or Pre RP PSA level ≥20 ng/mL, and/or Primary tumour stage 3a (pT3a) (with any PSA level and any Gleason score)
- Post-RP PSA levels ≤0.2 ng/mL at 6 weeks
- Evidence of lymph nodes or distant metastasis
- Positive margins
- Evidence of any other malignant disease, not treated with a curative intent
- Had surgical castration
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Triptorelin, 11.25 mg Triptorelin 11.25 mg Triptorelin, powder and solvent for suspension (prolonged released form)
- Primary Outcome Measures
Name Time Method Number of Subjects With BR Events Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). The primary efficacy analyses of Biochemical Relapse-Free Survival (BRFS) was performed after 61 BR events were observed on the study global level. The number of subjects with BR events per treatment group is reported. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later.
Median Time to BRFS Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or first quartile (Q1) (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports median time to BRFS (with Q1 time to BRFS reported in the subsequent outcome measure).
Q1 Time to BRFS Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). BRFS was defined as the time from randomisation to time of BR. The definition of BR was increased PSA \>0.2 ng/mL confirmed by a second measurement performed 4 to 6 weeks later. The time point at which the first elevated PSA measurement \>0.2 ng/mL was recorded was deemed to be the time of BR. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to BRFS associated with each treatment. This outcome measure reports Q1 time to BRFS.
- Secondary Outcome Measures
Name Time Method Median Time to Event-Free Survival (EFS) Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports median time to EFS (with Q1 time to EFS reported in the subsequent outcome measure).
Q1 Time to EFS Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). EFS was defined as the time from randomisation to time of first clinical disease progression or death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to EFS associated with each treatment. This outcome measure reports Q1 time to EFS.
Q1 Time to PSADT Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports Q1 time to PSADT.
Change From Baseline in Serum Testosterone Levels Baseline (Day 1) and Months 3, 6 and 9. Serum testosterone levels were evaluated on blood samples taken before triptorelin injection at baseline and at 3, 6 and 9 months only in subjects in the triptorelin arm. Change from baseline in testosterone levels are reported as median values at Months 3, 6 and 9. Note: the raw baseline values for testosterone levels are reported in the Baseline Characteristics section.
Median Time to Overall Survival (OS) Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports median time to OS (with Q1 time to OS reported in the subsequent outcome measure).
Q1 Time to OS Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). OS was defined as the time between randomisation and death from any cause. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) time to OS associated with each treatment. This outcome measure reports Q1 time to OS.
Time to Disease-specific Mortality Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). Disease-specific mortality was measured as the time between randomisation and death related to prostate cancer.
Median Time to PSA Doubling Time (PSADT) Baseline (Day 1) and every 3 months until end of study with final analysis performed after required 61 BRs were observed on global study level. Minimum monitoring period of 36 months for each subject; maximum duration of 78 months (last subject censored). PSADT was defined as the time from the first documented PSA increase \>0.2 ng/mL to the time of the first value more than twice that of the first increased value. The Kaplan-Meier method was used to obtain the estimates of median and/or Q1 (if median was not reached) PSADT associated with each treatment. This outcome measure reports median time to PSADT (with Q1 time to PSADT reported in the subsequent outcome measure).
Percent Change From Baseline in PSA Levels Screening (Day -14) and Months 3, 6, 9, 12, 24 and 36. As per inclusion criterion, all subjects in both treatment groups had PSA levels ≤0.2 ng/mL at the screening visit. Starting from Month 3, any elevated PSA concentration \>0.2 ng/mL had to be confirmed by a second measurement performed 4 to 6 weeks later. No confirmation test was required after evidence of disease progression (BR and/or clinical disease progression). Subjects remained in the study until Month 36, even if they had a biochemical failure (PSA levels \>0.2 ng/mL); then they could enter follow-up. The percent change from baseline was defined as the percent change from the screening visit (Day -14). Percent change from baseline in PSA levels are reported as median values at Months 3, 6, 9, 12, 24 and 36. Note: the raw baseline values for PSA levels are reported in the Baseline Characteristics section.
Change From Baseline in FACT-P Total Score Baseline (Day 1) and Months 9, 24 and 36. Health-Related Quality of Life (HRQoL) was assessed using the FACT-P questionnaire (v4) at baseline and at 9, 24 and 36 months. The FACT-P score is composed of 27 general questions about physical, social, emotional, and functional well-being, as well as a 12-item questionnaire about prostate-specific concerns. The total FACT-P score was calculated as the sum of 39 item scores (range of 0-156); higher scores indicate a better quality of life. Change from baseline in FACT-P total score are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for FACT-P total score are reported in the Baseline Characteristics section.
Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) Baseline (Day 1) and Months 9, 24 and 36. HRQoL was assessed using the SF-36 health survey (v2) at baseline and at 9, 24 and 36 months. The 36 items cover 8 health domains: PF, role-physical, BP, SF, MH, RE, VT and GH. Subscale scores were normed to the 2009 US general population (mean=50; SD=10) to give norm-based scores. Two summary measures were then calculated: PCS was derived from PF, role-physical, BP and GH; MCS was derived from SF, MH, RE and VT. The PCS and MCS norm-based scores ranged 0-100; higher scores indicate a better QoL. Change from baseline in SF-36 PCS and MSC norm-based scores are reported as mean values at Months 9, 24 and 36. A negative change from baseline indicates decreased QoL. Note: the raw baseline values for PCS and MSC norm-based scores are reported in the Baseline Characteristics section.
Trial Locations
- Locations (18)
Chinese PLA General HospitalDepartment of UrologySite #156007
🇨🇳Beijing, China
West China Hosspital, Sichuan UniversityDepartment of Urology Site #156008
🇨🇳Chengdu, China
The First Affiliated Hospital of the 3th Military Medical University of PLA (Southwest Hospital) Site # 156010
🇨🇳Chongqing, China
Peiking University First Hospital Site #156011
🇨🇳Beijing, China
The first hospital affiliated to medical school of Zhejiang university Site #156001
🇨🇳Hangzhou, China
Fudan University cancer hospital Site #156003
🇨🇳Shanghai, China
First Affiliated Hospital of the Fourth Military Medical University Site #156004
🇨🇳Xi'an, China
SUN YAT-SEN Cancer Center Department of Site #156009
🇨🇳Guangzhou, China
FSBI Russian Oncological Scientific Center named after N.N. Blokhina of RAMS, 23 Site #643001
🇷🇺Moscow, Russian Federation
FSI Moscow Research Oncological Institute named after P.A.Gertsen Site #643003
🇷🇺Moscow, Russian Federation
Budgetary Health care Institution of Omsk region "Clinical oncological dispensary" Site #643007
🇷🇺Omsk, Russian Federation
SIH Altaian Territorial Oncological Dispensary Site #643006
🇷🇺Barnaul, Russian Federation
The third hospital affiliated to Sun Yat-sen University Site #156005
🇨🇳Guangzhou, China
SBHI Sverdlovskaya Regional Clinical Hospital #1 Site #643004
🇷🇺Ekaterinburg, Russian Federation
FSBI "Research Institute of Urology" of Ministry of health care of Russia Site #643002
🇷🇺Moscow, Russian Federation
State Budgetary Healthcare Institution "Moscow Clinical Scientific-Practical Center named after A. S. Loginov of Healthcare Department of Moscow" Site #643009
🇷🇺Moscow, Russian Federation
Federal State Budgetary Health care Institution "Central clinical hospital of Russian Academy of Science (CCH RAS), in-patient unit, urological department Site #643005
🇷🇺Moscow, Russian Federation
Medical radiology research center named after A.F. Tsyba - branch of FSBI "National Medical Research Center of Radiology" of Ministry of healthcare of Russian Federation Site #643008
🇷🇺Obninsk, Russian Federation