Prostate Cancer
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to assess two treatment strategies (leuprorelin treatment and active surveillance without androgen deprivation) for indolent prostate cancer and to compare their therapeutic benefit for management of patients with low-risk, localized prostate cancer.
Detailed description
The drug being tested in this study is called leuprorelin. Leuprorelin is being tested to treat people who have prostate cancer. Study assessments will include adverse events, prostatic-specific antigen (PSA) levels, and prostate biopsies. The study will enroll approximately 120 patients. Participants will be randomly assigned (by chance, like flipping a coin) to a treatment group that will receive leuprorelin 11.25 mg (as one injection) or to an untreated observation group. Patients in the leuprorelin group will also receive bicalutamide 50 mg, a non-steroidal antiandrogen, once daily for 15 days to prevent a flare-up. This multi-center trial will be conducted in France. The overall time to participate in this study is 12 months. After the screening visit, participants will make 6 visits to the clinic.
Interventions
DRUGLeuprorelin
Solution for injection
DRUGBicalutamide
Bicalutamide tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Is an out-patient 50 to 80 years old. 2. Has read, understood, signed and dated the informed consent. 3. Has indolent prostate cancer defined by: * Clinical Stage T1c or T2a. * Biopsy cores of which at least 12 reveal the presence of positive cores and the absence of cores with tumor length \> 3 mm. * Absence of Grade 4 cells (Gleason \<7). * Prostate specific antigen (PSA) levels \<10 ng/ml. 4. Has a life expectancy \> 5 years. 5. Has accepted the principle of active surveillance. 6. Is willing to participate in the study for a minimum of fifteen months.
Exclusion criteria
1. Has prior androgen deprivation including a 5-alpha reductase inhibitor (finasteride or dutasteride) within the last 6 months. 2. Has psychological failure related to prostate cancer therapy. 3. Has any active disorder likely to affect the conduct of the study or the patient's prognosis during the study. 4. Has a mental deficiency or any other reason that may hinder the understanding or strict application of the protocol. 5. Is under judicial protection, tutorship or curatorship. 6. Is unlikely to attend control visits. 7. Is currently enrolled in an investigational study or has participated in another investigational study within the last 3 months. 8. Has an allergy or hypersensitivity to any components of leuprorelin (Enantone LP) 11.25 mg or Casodex® 50 mg. 9. Has a medical history of severely impaired hepatic function linked to bicalutamide or a pathological cause. 10. Has testosterone level \< 0.5 ng/ml.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Negative Biopsies at Month 12 | Month 12 | Staging biopsy of at least 12 cores were sampled and analyzed according to a centralized biopsy procedure which confirm the results of the first biopsy \[presence of positive cores, the absence of core with tumor length \> 3 millimeters (mm), and absence Grade 4 cells (Gleason score \< 7)\]. The Gleason score grades prostate cancer tissue, based on its appearance under a microscope. Scores range from 2 to 10, with a higher score meaning that the cancer tissue is more likely to spread. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Baseline and Months 3, 6, 9 and 12 | The I-PSS is an 8-question tool used to measure prostate symptoms (≤7: mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic). The first 7 symptom questions answered on a scale of 0 (never) to 5 (almost always) are used to determine the I-PSS Total S Score for a total possible score of 0 to 35. The 8th question is quality of life and is not reported here. A negative change from baseline indicates improvement. An Analysis of Covariance (ANCOVA) model fitted with baseline I-PSS total score and age as covariates was used for analysis. |
| Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI) | Baseline and Month 12 | MRI is an imaging technique used to investigate the anatomy and function of the body. Measurements were taken to calculate the prostatic volume in cubic millimeters (mm\^3). |
| Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI | Baseline and Month 12 | MRI is an imaging technique used to investigate the anatomy and function of the body. Measurements were taken to determine the diameter of the lesions in millimeters (mm). |
| Number of Participants With Gleason Score ≥ 7 | Month 12 | Gleason score grades prostate cancer tissue, based on its appearance under a microscope. Scores range from 2 to 10, with a higher score meaning that the cancer tissue is more likely to spread. |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Baseline and Months 3, 6, 9 and 12 | The HADS is a 14-item scale that measures anxiety (7-items) and depression (7-items) over the previous week. Each question is answered on a scale of 0 (best) to 3 (worst) for a total possible score of 0 to 42, with higher scores indicating more anxiety and depression. A negative change from baseline indicates improvement. An ANCOVA model fitted with baseline HADS score and age as covariates was used for analyses. |
| Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Baseline and Months 3, 6, 9 and 12 | The IIEF-5, a 5 question patient completed questionnaire, is a measure of erectile dysfunction over the past 6 months. Each question is answered on a scale of 1 (worst) to 5 (best). Total score ranges from 5 to 25 with higher scores indicating better function (5-7: severe; 8-11: moderate; 12-16: mild to moderate;17-21: mild; 22-25: none). A positive change from baseline indicates improvement. A negative change from baseline indicates a worsening. An ANCOVA model fitted with baseline IIEF-5 score and age as covariates was used for analyses. |
| Change From Baseline in Prostate-specific Antigen (PSA) Levels | Baseline and Months 3, 6, 9 and 12 | Blood was collected and sent to a central laboratory for analysis of PSA reported in milligrams/milliliter (mg/mL). A negative change from baseline indicates improvement. An ANCOVA model fitted with baseline PSA Level and age as covariates was used for analyses. |
Countries
France
Participant flow
Recruitment details
Participants took part in the study at 22 investigative sites in France from 03 June 2013 to 08 November 2016.
Pre-assignment details
Participants with a diagnosis of Prostate Cancer were randomised equally to one of two arms: leuprorelin 11.25 mg or active surveillance. 116 participants were randomized but 1 patient was excluded due to absence of prostate cancer before treatment.
Participants by arm
| Arm | Count |
|---|---|
| Leuprorelin 11.25 mg Active surveillance after a single subcutaneous injection of leuprorelin 11.25 mg and bicalutamide 50 mg, tablet, orally, once daily, to prevent flare-up for 15 days. | 58 |
| Active Surveillance Active surveillance is close medical monitoring of prostate cancer for any changes. | 57 |
| Total | 115 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Discontinuation Due to Patient Decision | 0 | 1 |
| Overall Study | Reason Not Specified | 0 | 1 |
| Overall Study | Reason Unknown | 0 | 1 |
| Overall Study | Withdrawal of Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Leuprorelin 11.25 mg | Active Surveillance | Total |
|---|---|---|---|
| Age, Continuous | 66.22 years STANDARD_DEVIATION 5.76 | 63.60 years STANDARD_DEVIATION 5.56 | 64.92 years STANDARD_DEVIATION 5.79 |
| Height | 171.85 centimeters (cm) STANDARD_DEVIATION 6.55 | 173.69 centimeters (cm) STANDARD_DEVIATION 8.08 | 172.77 centimeters (cm) STANDARD_DEVIATION 7.38 |
| Region of Enrollment France | 58 Participants | 57 Participants | 115 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 58 Participants | 57 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 40 / 58 | 11 / 57 |
| serious Total, serious adverse events | 4 / 58 | 3 / 57 |
Outcome results
Primary
Number of Participants With Negative Biopsies at Month 12
Staging biopsy of at least 12 cores were sampled and analyzed according to a centralized biopsy procedure which confirm the results of the first biopsy \[presence of positive cores, the absence of core with tumor length \> 3 millimeters (mm), and absence Grade 4 cells (Gleason score \< 7)\]. The Gleason score grades prostate cancer tissue, based on its appearance under a microscope. Scores range from 2 to 10, with a higher score meaning that the cancer tissue is more likely to spread.
Time frame: Month 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised. Participants with missing biopsy results have been excluded from the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Leuprorelin 11.25 mg | Number of Participants With Negative Biopsies at Month 12 | 28 Participants |
| Active Surveillance | Number of Participants With Negative Biopsies at Month 12 | 17 Participants |
Comparison: The null hypothesis was that there was no difference between the two treatment strategies.p-value: 0.0318Chi-squared
Secondary
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score
The HADS is a 14-item scale that measures anxiety (7-items) and depression (7-items) over the previous week. Each question is answered on a scale of 0 (best) to 3 (worst) for a total possible score of 0 to 42, with higher scores indicating more anxiety and depression. A negative change from baseline indicates improvement. An ANCOVA model fitted with baseline HADS score and age as covariates was used for analyses.
Time frame: Baseline and Months 3, 6, 9 and 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Leuprorelin 11.25 mg | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 3 | -0.83 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 6 | -1.44 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 9 | -2.06 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 12 | -1.87 score on a scale |
| Active Surveillance | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 12 | -1.95 score on a scale |
| Active Surveillance | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 3 | -1.20 score on a scale |
| Active Surveillance | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 9 | -1.76 score on a scale |
| Active Surveillance | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Score | Change at Month 6 | -1.58 score on a scale |
Secondary
Change From Baseline in Prostate-specific Antigen (PSA) Levels
Blood was collected and sent to a central laboratory for analysis of PSA reported in milligrams/milliliter (mg/mL). A negative change from baseline indicates improvement. An ANCOVA model fitted with baseline PSA Level and age as covariates was used for analyses.
Time frame: Baseline and Months 3, 6, 9 and 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Leuprorelin 11.25 mg | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 3 | -4.61 mg/mL |
| Leuprorelin 11.25 mg | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 6 | -3.27 mg/mL |
| Leuprorelin 11.25 mg | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 9 | -1.46 mg/mL |
| Leuprorelin 11.25 mg | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 12 | 0.17 mg/mL |
| Active Surveillance | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 12 | 0.76 mg/mL |
| Active Surveillance | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 3 | 0.22 mg/mL |
| Active Surveillance | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 9 | 0.71 mg/mL |
| Active Surveillance | Change From Baseline in Prostate-specific Antigen (PSA) Levels | Change at Month 6 | 0.85 mg/mL |
Secondary
Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score
The IIEF-5, a 5 question patient completed questionnaire, is a measure of erectile dysfunction over the past 6 months. Each question is answered on a scale of 1 (worst) to 5 (best). Total score ranges from 5 to 25 with higher scores indicating better function (5-7: severe; 8-11: moderate; 12-16: mild to moderate;17-21: mild; 22-25: none). A positive change from baseline indicates improvement. A negative change from baseline indicates a worsening. An ANCOVA model fitted with baseline IIEF-5 score and age as covariates was used for analyses.
Time frame: Baseline and Months 3, 6, 9 and 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Leuprorelin 11.25 mg | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 3 | -7.40 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 6 | -5.87 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 9 | -1.94 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 12 | -1.68 score on a scale |
| Active Surveillance | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 12 | -0.02 score on a scale |
| Active Surveillance | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 3 | 0.00 score on a scale |
| Active Surveillance | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 9 | -0.38 score on a scale |
| Active Surveillance | Change From Baseline in the International Index of Erectile Function (IIEF-5) Questionnaire Score | Change at Month 6 | 0.01 score on a scale |
Secondary
Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score
The I-PSS is an 8-question tool used to measure prostate symptoms (≤7: mildly symptomatic; 8-19 moderately symptomatic; 20-35 severely symptomatic). The first 7 symptom questions answered on a scale of 0 (never) to 5 (almost always) are used to determine the I-PSS Total S Score for a total possible score of 0 to 35. The 8th question is quality of life and is not reported here. A negative change from baseline indicates improvement. An Analysis of Covariance (ANCOVA) model fitted with baseline I-PSS total score and age as covariates was used for analysis.
Time frame: Baseline and Months 3, 6, 9 and 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Leuprorelin 11.25 mg | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 3 | 0.37 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 6 | -0.38 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 9 | -1.13 score on a scale |
| Leuprorelin 11.25 mg | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 12 | -0.48 score on a scale |
| Active Surveillance | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 12 | 0.93 score on a scale |
| Active Surveillance | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 3 | 1.03 score on a scale |
| Active Surveillance | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 9 | 0.64 score on a scale |
| Active Surveillance | Change From Baseline in the International Prostate Symptom Score (I-PSS) Total Symptom (S) Score | Change at Month 6 | 0.32 score on a scale |
Secondary
Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI
MRI is an imaging technique used to investigate the anatomy and function of the body. Measurements were taken to determine the diameter of the lesions in millimeters (mm).
Time frame: Baseline and Month 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomized and for whom MRI was performed. Participants with missing MRI data are excluded from analyses. Number analyzed is the number of participants with diameter data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprorelin 11.25 mg | Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI | Baseline | 6.39 mm | Standard Deviation 2.8 |
| Leuprorelin 11.25 mg | Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI | Month 12 | 6.25 mm | Standard Deviation 3.62 |
| Active Surveillance | Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI | Baseline | 7.78 mm | Standard Deviation 2.02 |
| Active Surveillance | Highest Diameter of the Lesion as a Measure of Tumor Radiologic Progression Using Dynamic MRI | Month 12 | 7.69 mm | Standard Deviation 2.56 |
Secondary
Number of Participants With Gleason Score ≥ 7
Gleason score grades prostate cancer tissue, based on its appearance under a microscope. Scores range from 2 to 10, with a higher score meaning that the cancer tissue is more likely to spread.
Time frame: Month 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised. Participants with missing Gleason score data are excluded.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Leuprorelin 11.25 mg | Number of Participants With Gleason Score ≥ 7 | 1 Participants |
| Active Surveillance | Number of Participants With Gleason Score ≥ 7 | 3 Participants |
Secondary
Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI)
MRI is an imaging technique used to investigate the anatomy and function of the body. Measurements were taken to calculate the prostatic volume in cubic millimeters (mm\^3).
Time frame: Baseline and Month 12
Population: Full Analysis Set included all participants with prostate cancer who signed informed consent and were randomised. Participants with missing MRI data are excluded from analyses. Number analyzed is the number of participants with prostatic volume data at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Leuprorelin 11.25 mg | Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI) | Baseline | 48.48 mm^3 | Standard Deviation 25.09 |
| Leuprorelin 11.25 mg | Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI) | Month 12 | 51.47 mm^3 | Standard Deviation 28.15 |
| Active Surveillance | Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI) | Baseline | 49.44 mm^3 | Standard Deviation 25.88 |
| Active Surveillance | Prostatic Volume as a Measure of Tumor Radiologic Progression Using Dynamic Magnetic Resonance Imaging (MRI) | Month 12 | 48.33 mm^3 | Standard Deviation 20.18 |