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.

Study Overview
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Brief Summary
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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
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This trial is a phase IV (in Russia and China) as approved indication is locally advanced or metastatic prostate cancer in both countries.

Official Title
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A Multicentric, Multinational (China and Russia), Randomised, Open, Controlled 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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Triptorelin 11.25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Evidence of lymph nodes or distant metastasis Positive margins Evidence of any other malignant disease, not treated with a curative intent Had surgical castration

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Triptorelin, 11.25 mg<br>Triptorelin, powder and solvent for suspension (prolonged released form) | Drug: Triptorelin 11.25 mg<br>* Triptorelin, one injection every 3 months. A total of 3 injections (at baseline, 3 and 6 months)<br>|
| No Intervention: Active surveillance<br>Active surveillance after radical prostatectomy (RP) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With BR Events | 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. | 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). | 
| Median Time to BRFS | 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). | 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). | 
| Q1 Time to BRFS | 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. | 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). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Event-Free Survival (EFS) | 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). | 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). | 
| Q1 Time to EFS | 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. | 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). | 
| Median Time to Overall Survival (OS) | 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). | 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). | 
| Q1 Time to OS | 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. | 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). | 
| Time to Disease-specific Mortality | Disease-specific mortality was measured as the time between randomisation and death related to prostate cancer. | 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). | 
| Median Time to PSA Doubling Time (PSADT) | 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). | 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). | 
| Q1 Time to PSADT | 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. | 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). | 
| Percent Change From Baseline in PSA Levels | 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. | Screening (Day -14) and Months 3, 6, 9, 12, 24 and 36. | 
| Change From Baseline in Serum Testosterone Levels | 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. | Baseline (Day 1) and Months 3, 6 and 9. | 
| Change From Baseline in FACT-P Total Score | 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. | Baseline (Day 1) and Months 9, 24 and 36. | 
| Change From Baseline in SF-36 Physical and Mental Component Summary Measures Norm-Based Scores (i.e. PCS and MCS) | 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. | Baseline (Day 1) and Months 9, 24 and 36. |