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

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Leuprorelin; Drug: Bicalutamide

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Paris, France, 75020
    • Tenon Hospital Paris France
  • Paris, France, 92977
    • Ouzid, Paris La Défense,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Leuprorelin; Solution for injection; Other Names: Enantone ®; Drug: Bicalutamide; Bicalutamide tablets; Other Names: Casodex ®
No Intervention: Active surveillance; Active surveillance is close medical monitoring of prostate cancer for any changes.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2013
• Primary Completion (Actual): November 8, 2016
• Study Completion (Actual): November 8, 2016

Study Registration Dates

• First Submitted: July 24, 2013
• First Submitted That Met QC Criteria: March 11, 2014
• First Posted (Estimate): March 12, 2014

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgen Antagonists; Leuprolide; Bicalutamide
• Other Study ID Numbers: FR-LEU-002; 2012-002653-35 (EudraCT Number); U1111-1146-5402 (Registry Identifier: WHO)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No