Effects of Triptorelin When Given Every 6-months Under the Skin to Adult Males With Cancer in the Prostate

Study Overview
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Brief Summary
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The aim of the study is to determine if triptorelin formulated for use every 6 months (given twice during the study) is effective and safe for when given by injection under the skin for the treatment of adult males with cancer in the prostate.

Official Title
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An Open-label, Multicentre, Single Arm Study to Assess the Efficacy and Safety of Triptorelin 6-month Formulation Administered Subcutaneously in Participants With Locally Advanced and/or Metastatic Prostate Cancer Previously Treated and Castrated With a GnRH Analogue

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Triptorelin embonate 22.5 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : Participant is male and must be 18 years of age inclusive, at the time of signing the informed consent Participant has histologically or cytologically proven prostate cancer with rising PSA after failed local therapy or metastatic disease, or requiring radiotherapy, and be a candidate for long-term (i.e. >1 year) androgen deprivation therapy Participant requires a GnRH analogue treatment for a minimum of 18 months, of which a minimum of 3 months of GnRH analogue treatment has already been provided prior to screening. (Note: participants must receive study intervention on Day 1 in accordance with the treatment schedule of their previously received GnRH analogue therapy). Has serum testosterone levels <1.735 nmol/L (50 ng/dL) at screening Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 Has a life expectancy of >18 months Male participants must agree that, if their partner is at risk of becoming pregnant (although highly unlikely in this study population), they will use an effective method of contraception. The participant must agree to use the contraception during the whole of the study and for 9 months after the last dose of study intervention Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol Exclusion Criteria : Presence of another neoplastic lesion or brain metastases Metastatic hormone-sensitive prostate cancer with high tumour burden Metastatic castration-resistant prostate cancer Any concomitant disorder or resulting therapy that is likely to interfere with participant compliance or with the study in the opinion of the investigator Use of finasteride (Proscar®) or dutasteride (Avodart®/Avolve®) within the past 6 months Planned intermittent scheme of GnRH analogue At the time of screening, planned use of any chemotherapy for prostate cancer during the study Prior hypophysectomy or adrenalectomy Participation in another study with an experimental drug within 3 months before signing informed consent or within five half-lives of the investigational drug (whichever was the longer), or any other type of medical research Severe kidney or liver failure (creatinine >2 times the normal range, aspartate aminotransferase and alanine aminotransferase >3 times the normal range) Any concomitant disorder or resulting therapy that is likely to interfere with participant's compliance, the subcutaneous administration of the drug or with the study in the opinion of the investigator Previous history of QT prolongation or concomitant use of medicinal products known to prolong the QT interval or with a known risk of torsades de pointes Known hypersensitivity to triptorelin or any of its excipients, GnRH, other GnRH agonist/analogues Known active use of recreational drug or alcohol dependence in the opinion of the investigator Inability to give informed consent or to comply fully with the protocol

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triptorelin embonate<br>All participants will receive triptorelin embonate 22.5 mg | Drug: Triptorelin embonate 22.5 mg<br>* A prolonged release formulation of triptorelin pamoate 22.5 mg 6-month formulation in D, L-lactide-co-glycolide polymers for single subcutaneous injection on Day 1 and Day 169<br>* Other names: Decapeptyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 29 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 85 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 141 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 169 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 253 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 309 | 
| Percentage of participants maintaining castrate levels of serum testosterone | The percentage of participants remaining castrated (maintenance of castration defined as testosterone <1.735 nmol/L (50 ng/dL) at Day 29, Day 85, Day 141, Day 169, Day 253, Day 309 and Day 337) during the study. | At day 337 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants castrated | Serum will be analysed to determine concentrations of testosterone using a validated, specific and sensitive liquid chromatography tandem mass spectrometry methods Castration defined as testosterone <1.735 nmol/L (50 ng/dL)). | Day 29, Day 85, Day 141, Day 169, Day 253, Day 309, Day 337 | 
| Percentage of participants with a serum testosterone level <0.694 nmol/L (20 ng/dL) |  | From baseline to Week 52 | 
| Percentage of participants with a serum testosterone level <0.69 nmol/L (20 ng/dL) |  | Day 29, Day 85, Day 141, Day 169, Day 253, Day 309, Day 337 | 
| Percentage of participants castrated | Serum will be analysed to determine concentrations of testosterone using a validated, specific and sensitive liquid chromatography tandem mass spectrometry methods. Castration defined as testosterone <1.735 nmol/L (50 ng/dL)). | Day 3 and Day 7 after each injection administered on Day 1 and Day 169 | 
| Percent change in Prostate Specific Antigen | Defined as the absolute value of difference between the PSA values at each timepoint and the baseline value divided by the baseline value. Blood samples will be analysed to determine concentrations of PSA. | Baseline, Day 169 and Day 337 | 
| Incidence of treatment-emergent adverse events (including local tolerability) | All adverse events and serious adverse events will be collected from the signing of the informed consent form until the end of the study. | Up to Day 337 | 
| Change in clinical safety laboratory blood chemistry parameters | Number of abnormal laboratory parameters (creatinine, glucose, ALT, AST, alkaline phosphatase, total and conjugated bilirubin) or other safety assessments, including those that worsen from baseline and if clinically significant by investigator's judgment. | Baseline and Day 337 | 
| Change in clinical safety laboratory haematology parameters | Number of abnormal laboratory parameters (WBC and differential count, platelet count, Hb) or other safety assessments, including those that worsen from baseline and if clinically significant by investigator's judgment. | Baseline and Day 337 | 
| Change in physical examination | Number of abnormal physical examination (cardiovascular, respiratory, gastrointestinal and neurological systems, Height and weight) including those that worsen from baseline and if clinically significant by investigator's judgment. | Baseline, Day 169, and Day 337 | 
| Change in electrocardiogram (ECG) | A single 12-lead ECG will be recorded so that the different ECG intervals (RR, PR, QRS, QT, QTcF) can be measured automatically. The ECG will be recorded with the participant in supine position after five minutes of rest until four regular consecutive complexes are available. | Baseline and Day 337 | 
| Change in heart rate | Heart rate will be assessed with an automated device so that measurements are independent of the observer. Heart rate will be recorded after 5 minutes rest in supine position. Absolute values and change from Baseline will be analysed. | Baseline and at each visit up to Day 337 | 
| Change in blood pressure | Blood pressure will be assessed with an automated device so that measurements are independent of the observer. Blood pressure will be recorded after 5 minutes rest in supine position. Absolute values and change from Baseline will be analysed. | Baseline and at each visit up to Day 337 |