A Study of the Effect of Enantone LP 11.25 mg (Leuprorelin) on the Histological Progression of Indolent Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label, Multicenter, Phase III Study to Assess the Impact of Transient Androgenic Deprivation With Enantone LP 11.25 Mg (Leuprorelin) on the Histological Progression of Indolent Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Leuprorelin
* Drug: Bicalutamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is an out-patient 50 to 80 years old. Has read, understood, signed and dated the informed consent. 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. Has a life expectancy > 5 years. Has accepted the principle of active surveillance. Is willing to participate in the study for a minimum of fifteen months. Exclusion Criteria: Has prior androgen deprivation including a 5-alpha reductase inhibitor (finasteride or dutasteride) within the last 6 months. Has psychological failure related to prostate cancer therapy. Has any active disorder likely to affect the conduct of the study or the patient's prognosis during the study. Has a mental deficiency or any other reason that may hinder the understanding or strict application of the protocol. Is under judicial protection, tutorship or curatorship. Is unlikely to attend control visits. Is currently enrolled in an investigational study or has participated in another investigational study within the last 3 months. Has an allergy or hypersensitivity to any components of leuprorelin (Enantone LP) 11.25 mg or Casodex® 50 mg. Has a medical history of severely impaired hepatic function linked to bicalutamide or a pathological cause. Has testosterone level < 0.5 ng/ml.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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 |
| --- | --- |
| Experimental: Leuprorelin 11.25 mg<br>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. | Drug: Leuprorelin<br>* Solution for injection<br>* Other names: Enantone ®;Drug: Bicalutamide<br>* Bicalutamide tablets<br>* Other names: Casodex ®;|
| No Intervention: Active surveillance<br>Active surveillance is close medical monitoring of prostate cancer for any changes. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Month 12 | 
| 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. | Baseline and Months 3, 6, 9 and 12 | 
| 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). | Baseline and Month 12 | 
| 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). | Baseline and Month 12 | 
| 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. | Baseline and Months 3, 6, 9 and 12 | 
| 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. | Baseline and Months 3, 6, 9 and 12 | 
| 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. | Baseline and Months 3, 6, 9 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy