Back to resultsLeuprorelin Associated With Radiotherapy Versus Leuprorelin Alone in T3 - T4 or pT3 (on Biopsy) N0, M0 Prostate Cancer
Primary Purpose
Prostatic Neoplasms, Locally Advanced
Status
Completed
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Leuprorelin SR
Radiotherapy
Flutamide
Sponsored by
About this trial
This is an interventional treatment trial for Prostatic Neoplasms, Locally Advanced focused on measuring Drug Therapy, Radiotherapy
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed locally advanced adenocarcinoma of the prostate, graded: T3 or T4 or pT3 on biopsies (presence of tumour tissue in periprostatic fat observed on biopsies), N0 (absence of metastatic), M0 (no distant metastases detectable on the following examinations: bone scan, chest x-ray, abdominal and pelvic ultrasound).
- Patient in whom the prostatic adenocarcinoma has received no prior treatment of any type, with the possible exception of transurethral resection due to obstructive symptoms.
- Patient with a Karnofsky index greater than or equal to (≥) 70.
- Patient aged under 80 years on the randomization date.
- Patient with a life expectancy of at least 7 years.
- Patient who, after having received clear information, gave his written consent to participate and cooperate in the study.
- Patient for whom a recent blood test (less than [<] 2 months) has not revealed elevated transaminases ≥ 3 times the normal laboratory range.
Exclusion Criteria:
- Patient incapable of understanding the information supplied concerning the study or of giving his consent, or having refused to sign the informed consent form,
- Patient for whom there is a risk that follow-up in compliance with the conditions stipulated by the protocol will not be possible,
- Patient having already received prior treatment for prostate cancer, excluding transurethral resection of the prostate to relieve obstruction,
- Patient having undergone surgical castration, or with a history of bilateral adrenalectomy or hypophysectomy,
- Patient having had another cancer within the previous 5 years (including carcinoma in situ of the bladder) excluding basocellular epithelioma or carcinoma in situ (other than in the bladder),
- Patient with lymph node or metastatic spread of the prostatic adenocarcinoma suspected on imaging,
- Patient with a non-controlled severe active disease,
- Patient with a contraindication to external prostatic radiotherapy,
- Patient receiving or having received another experimental treatment within 3 months prior to inclusion in the study,
- Patient with impaired liver function or elevated transaminases ≥3 times the normal laboratory range.
Sites / Locations
- Clinique Mutualiste
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Combined Radiotherapy and Hormone Therapy
Hormone Therapy alone
Arm Description
Leuprorelin 11.25 milligram (mg) sustained release (SR), injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin. Radiotherapy 70 +/- 4 Gray (Gy) in 35 fractions at a rate of 5 fractions of 2 Gy per week up to 3 years. An interval of a maximum of 2 weeks is authorized between radiation of the pelvis with 50 Gy (±4) (5 weeks) and radiation of the prostate with an additional 20 Gy.
Leuprorelin 11.25 mg SR, injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin.
Outcomes
Primary Outcome Measures
Progression-free survival at 5 years
PFS=time from randomization to first documentation of progression (death, biological progression or clinical progression). PFS at Year 5=probability of participants' PFS at Year 5. Biological progression definition I: halfway point between nadir and first rise with prostate-specific antigen (PSA) ≥1 nanogram per milliliter (ng/mL) signifying progression and date of introduction of prostate treatment for all participants, including those leaving prematurely for reason other than progression/death; definition II: first date when PSA=nadir+2 ng/mL and date of introduction of prostate treatment, for participants leaving prematurely for reason other than progression/death. Clinical progression: local clinical progression->50% increase in prostate volume relative to lowest volume, recurrence of palpable prostatic tumor after complete regression, positive biopsy; locoregional progression=pelvic regional lymph node lesion development; metastatic progression=distant lesions identification.
Secondary Outcome Measures
Time to Biological Progression
Biological progression as per definition I is defined as halfway point between nadir and first rise with PSA greater than or equal to (≥) 1 ng/mL signifying progression and date of introduction of prostate treatment for all participants, including those leaving prematurely for reason other than progression/death; and as per definition II, it is defined as first date when PSA=nadir+2 ng/mL and date of introduction of prostate treatment, for participants leaving prematurely for reason other than progression/death. Time to onset of biological progression will be performed using the Kaplan- Meier method taking into account the date of onset of the first biological progression. The participants will be censored on the date of death, lost to follow-up or living without biological progression on the date of the last news.
Time to Clinical Progression
Clinical progression is based on three parameters: local clinical progression which is defined as greater than (>) 50 percent (%) increase in prostate volume relative to lowest volume, recurrence of palpable prostatic tumor after complete regression, positive biopsy; locoregional progression which is defined as pelvic regional lymph node lesion development; and metastatic progression which is defined as distant lesions identification. Time to onset of clinical progression will be performed using the Kaplan-Meier method based on the date of onset of the first progression among local, locoregional or metastatic clinical progressions.
Overall Survival
Overall survival will be measured as the time from the date of randomization to the date of death. Participants will be censored in case of lost to follow-up or alive on the date of the last news.
Time to Locoregional Progression
Locoregional progression is defined as the development of pelvic regional lymph node lesion(s) identified by computed tomography (CT) scan or ultrasound and confirmed by biopsy in the absence of any other signs of progression. It will be performed using the Kaplan-Meier method taking into account the date of onset of locoregional progression.
Time to Onset of Metastatic Progression
Metastatic progression is defined as identification of distant lesions. Time to onset of metastatic progression will be performed using the Kaplan-Meier method taking into account the date of onset of the first metastatic progression. The participants will be censored in case of death, lost to follow-up or alive without metastatic progression on the date of the last news.
Specific Survival
Analysis of specific survival using the Kaplan-Meier method takes into account the dates of death linked to the disease. The participants will be censored in case of death, lost to follow-up or alive on the date of the last news.
Number of Deaths linked to the disease
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01122121
Brief Title
Leuprorelin Associated With Radiotherapy Versus Leuprorelin Alone in T3 - T4 or pT3 (on Biopsy) N0, M0 Prostate Cancer
Official Title
Comparative Efficacy and Safety of Combined Radiotherapy and Adjuvant Hormone Therapy (Leuprorelin SR 11.25 mg) and Hormone Therapy Alone (Leuprorelin SR 11.25 mg) in Locally Advanced Prostate Cancer (T3-T4 or pT3 on Biopsy, N0, M0)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
March 2000 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the efficacy and safety of combined radiotherapy and hormone therapy and hormone therapy alone in the treatment of clinically locally advanced prostate cancer (T3-T4 or pT3 on biopsy, N0, M0).
Detailed Description
The drug being tested in this study is called leuprorelin SR. Leuprorelin SR is being tested to treat people who have prostate cancer. This study will look at the overall survival of people who take leuprorelin SR in addition to radiation therapy compared to those who take only leuprorelin SR.
The study will enroll approximately 273 patients. Participants will be randomly assigned to one of the two treatment groups.
Combined Radiotherapy and Hormone Therapy
Hormone Therapy alone. All participants will receive leuprorelin injection every 3 months and flutamide tablets thrice daily for first 30 days as part of hormone therapy. Participants randomized to combined radiotherapy and hormone therapy group, will also receive radiotherapy 70 +/- 4 Gy in 35 fractions at a rate of 5 fractions of 2 Gy per week.
This multi-center trial will be conducted in France and Tunisia. The overall time to participate in this study is 8 years. The scheduled duration of hormone therapy was 3 years in both arms, with an additional treatment-free follow-up period of 2 years i.e. a total follow-up period of 5 years. Post-protocol collection of information relative to survival will be performed after the end the 5-year follow-up period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostatic Neoplasms, Locally Advanced
Keywords
Drug Therapy, Radiotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
273 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Combined Radiotherapy and Hormone Therapy
Arm Type
Experimental
Arm Description
Leuprorelin 11.25 milligram (mg) sustained release (SR), injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin. Radiotherapy 70 +/- 4 Gray (Gy) in 35 fractions at a rate of 5 fractions of 2 Gy per week up to 3 years. An interval of a maximum of 2 weeks is authorized between radiation of the pelvis with 50 Gy (±4) (5 weeks) and radiation of the prostate with an additional 20 Gy.
Arm Title
Hormone Therapy alone
Arm Type
Active Comparator
Arm Description
Leuprorelin 11.25 mg SR, injection, subcutaneously, once every 3 months up to 3 years and flutamide 250 mg, tablet, orally, thrice daily for 30 days from the first dose of leuprorelin.
Intervention Type
Drug
Intervention Name(s)
Leuprorelin SR
Other Intervention Name(s)
ENANTONE SR
Intervention Description
Leuprorelin SR injection
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiotherapy 70 +/- 4 Gy
Intervention Type
Drug
Intervention Name(s)
Flutamide
Intervention Description
Flutamide tablets
Primary Outcome Measure Information:
Title
Progression-free survival at 5 years
Description
PFS=time from randomization to first documentation of progression (death, biological progression or clinical progression). PFS at Year 5=probability of participants' PFS at Year 5. Biological progression definition I: halfway point between nadir and first rise with prostate-specific antigen (PSA) ≥1 nanogram per milliliter (ng/mL) signifying progression and date of introduction of prostate treatment for all participants, including those leaving prematurely for reason other than progression/death; definition II: first date when PSA=nadir+2 ng/mL and date of introduction of prostate treatment, for participants leaving prematurely for reason other than progression/death. Clinical progression: local clinical progression->50% increase in prostate volume relative to lowest volume, recurrence of palpable prostatic tumor after complete regression, positive biopsy; locoregional progression=pelvic regional lymph node lesion development; metastatic progression=distant lesions identification.
Time Frame
Year 5
Secondary Outcome Measure Information:
Title
Time to Biological Progression
Description
Biological progression as per definition I is defined as halfway point between nadir and first rise with PSA greater than or equal to (≥) 1 ng/mL signifying progression and date of introduction of prostate treatment for all participants, including those leaving prematurely for reason other than progression/death; and as per definition II, it is defined as first date when PSA=nadir+2 ng/mL and date of introduction of prostate treatment, for participants leaving prematurely for reason other than progression/death. Time to onset of biological progression will be performed using the Kaplan- Meier method taking into account the date of onset of the first biological progression. The participants will be censored on the date of death, lost to follow-up or living without biological progression on the date of the last news.
Time Frame
Baseline up to Year 5
Title
Time to Clinical Progression
Description
Clinical progression is based on three parameters: local clinical progression which is defined as greater than (>) 50 percent (%) increase in prostate volume relative to lowest volume, recurrence of palpable prostatic tumor after complete regression, positive biopsy; locoregional progression which is defined as pelvic regional lymph node lesion development; and metastatic progression which is defined as distant lesions identification. Time to onset of clinical progression will be performed using the Kaplan-Meier method based on the date of onset of the first progression among local, locoregional or metastatic clinical progressions.
Time Frame
Baseline up to Year 5
Title
Overall Survival
Description
Overall survival will be measured as the time from the date of randomization to the date of death. Participants will be censored in case of lost to follow-up or alive on the date of the last news.
Time Frame
Baseline up to Year 5
Title
Time to Locoregional Progression
Description
Locoregional progression is defined as the development of pelvic regional lymph node lesion(s) identified by computed tomography (CT) scan or ultrasound and confirmed by biopsy in the absence of any other signs of progression. It will be performed using the Kaplan-Meier method taking into account the date of onset of locoregional progression.
Time Frame
Baseline up to Year 5
Title
Time to Onset of Metastatic Progression
Description
Metastatic progression is defined as identification of distant lesions. Time to onset of metastatic progression will be performed using the Kaplan-Meier method taking into account the date of onset of the first metastatic progression. The participants will be censored in case of death, lost to follow-up or alive without metastatic progression on the date of the last news.
Time Frame
Baseline up to Year 5
Title
Specific Survival
Description
Analysis of specific survival using the Kaplan-Meier method takes into account the dates of death linked to the disease. The participants will be censored in case of death, lost to follow-up or alive on the date of the last news.
Time Frame
Baseline up to Year 5
Title
Number of Deaths linked to the disease
Time Frame
Baseline up to Year 5
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed locally advanced adenocarcinoma of the prostate, graded: T3 or T4 or pT3 on biopsies (presence of tumour tissue in periprostatic fat observed on biopsies), N0 (absence of metastatic), M0 (no distant metastases detectable on the following examinations: bone scan, chest x-ray, abdominal and pelvic ultrasound).
Patient in whom the prostatic adenocarcinoma has received no prior treatment of any type, with the possible exception of transurethral resection due to obstructive symptoms.
Patient with a Karnofsky index greater than or equal to (≥) 70.
Patient aged under 80 years on the randomization date.
Patient with a life expectancy of at least 7 years.
Patient who, after having received clear information, gave his written consent to participate and cooperate in the study.
Patient for whom a recent blood test (less than [<] 2 months) has not revealed elevated transaminases ≥ 3 times the normal laboratory range.
Exclusion Criteria:
Patient incapable of understanding the information supplied concerning the study or of giving his consent, or having refused to sign the informed consent form,
Patient for whom there is a risk that follow-up in compliance with the conditions stipulated by the protocol will not be possible,
Patient having already received prior treatment for prostate cancer, excluding transurethral resection of the prostate to relieve obstruction,
Patient having undergone surgical castration, or with a history of bilateral adrenalectomy or hypophysectomy,
Patient having had another cancer within the previous 5 years (including carcinoma in situ of the bladder) excluding basocellular epithelioma or carcinoma in situ (other than in the bladder),
Patient with lymph node or metastatic spread of the prostatic adenocarcinoma suspected on imaging,
Patient with a non-controlled severe active disease,
Patient with a contraindication to external prostatic radiotherapy,
Patient receiving or having received another experimental treatment within 3 months prior to inclusion in the study,
Patient with impaired liver function or elevated transaminases ≥3 times the normal laboratory range.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas MOTTET, Dr
Organizational Affiliation
Clinique Mutualiste - Saint-Etienne
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pierre RICHAUD, Dr
Organizational Affiliation
Institut BERGONIÉ, Centre Régional de Lutte contre le Cancer, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michel PENEAU, Dr
Organizational Affiliation
Martinique
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jean-Jacques MAZERON, Pr
Organizational Affiliation
Groupe Hospitalier PITIE-SALPETRIERE, Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinique Mutualiste
City
Saint-etienne
ZIP/Postal Code
42013
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
30946523
Citation
Sargos P, Mottet N, Bellera C, Richaud P. Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. BJU Int. 2020 Jun;125(6):810-816. doi: 10.1111/bju.14768. Epub 2020 Mar 2.
Results Reference
derived
Learn more about this trial
Leuprorelin Associated With Radiotherapy Versus Leuprorelin Alone in T3 - T4 or pT3 (on Biopsy) N0, M0 Prostate Cancer
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