Induction and Maintenance of Castration After Subcutaneous Injections of Triptorelin Pamoate in Patients With Prostate Cancer (DKP 3M SC)

A Phase III Single Arm Study to Evaluate the Efficacy, Safety and Local Tolerability of a Subcutaneous 3-month Formulation of Triptorelin Pamoate (11.25 mg) in Patients With Locally Advanced or Metastatic Prostate Cancer

Assess the efficacy and safety of Triptorelin pamoate 3M formulation (11.25mg) when administered by subcutaneous route.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Triptorelin Pamoate 11.25mg

• Study Type: Interventional
• Enrollment (Actual): 126
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria
  • Plovdiv, Bulgaria
  • Shumen, Bulgaria
  • Varna, Bulgaria
• France
  • Suresnes, France
• Latvia
  • Daugavpils, Latvia
  • Riga, Latvia
• Poland
  • Kutno, Poland
  • Warsaw, Poland
  • Wroclaw, Poland
• Romania
  • Bucharest, Romania
  • Craiova, Romania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologically proven locally advanced or metastatic prostate cancer who are suitable for androgen deprivation therapy
• Male aged ≥18 years old
• Screening testosterone level of >125 ng/dL
• Life expectancy of greater than 12 months in the judgement of the Investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Willing to give signed informed consent freely
• Able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Prior hormonal therapy for prostate cancer
• Prior surgery or radiotherapy of prostate cancer with curative intent unless disease is verified by a rising prostate specific antigen (PSA) concentration on follow up (elevated PSA values on last two tests conducted at least a month apart) and the patient is eligible for androgen deprivation therapy
• Presence or history of any other malignancy except for non melanoma skin cancer adequately treated at least 2 years before study entry
• Painful local bone lesions or spinal lesions which may lead to compression
• History of myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, Class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within six months prior to start of study treatment and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and untreated atrial or uncontrolled ventricular arrhythmias
• Any condition in opinion of the Investigator, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could confound the ability to interpret data from the study, compromises the objective of the study or places the patient at unacceptable risk if he participates in the study

• Abnormal haematological, hepatic or renal functions:

  • Haemoglobin <9 g/dL, absolute neutrophil count ≤1.5 x 10^9/L or platelets ≤100 x 10^9/L
  • Serum creatinine ≥1.5 times the upper limit of normal (ULN)
  • Aspartate aminotransferase or alanine aminotransferase >2.5 times the ULN
• Known hypersensitivity to the study treatment, to any of its excipients
• Known active use of recreational drug or alcohol dependence in the opinion of the Investigator
• Any current use or use within six months prior to start of treatment, of medications which are known to affect the metabolism and/or secretion of androgenic hormones: e.g. ketoconazole, aminoglutethimide, oestrogens, and progesterone
• Use of systemic corticosteroids (inhaled corticosteroids and topical application of corticosteroids are permitted)
• Aged ≥90 years for the main study and ≥80 years for those included in the pharmacokinetic (PK) patient population
• Participation in any other study or receipt of any investigational compound in the 30 days (or five times the elimination half life if this is longer) prior to study entry
• Any skin or other condition that may preclude s.c. injection administration
• Known brain or epidural metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 11.25mg; 11.25mg, SC on Day 1 and Day 92	Drug: Triptorelin Pamoate 11.25mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Demonstrating Castration at Day 29 and Maintaining Castration at Day 183	Percentage of subjects castrated (i.e. with serum testosterone <50 ng/dL or 1.735 nmol/L, using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and the proportion with castration maintained at Day 183 (after receiving 2 S.C. administrations of triptorelin pamoate, three months apart); they were calculated along with their respective 95% confidence intervals (CI) using exact methods on the ITT population at Day 29 and on the initially castrated (IC) population at Day 183	At Day 29 and 183

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Demonstrating Castration Before Administration of the Second Dose	Percentage of subjects demonstrating castration at Day 92 (before administration of the second dose) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.	At Day 92
Probability of Testosterone <50 ng/dL	Probability of testosterone <50 ng/dL from Day 29 to Day 183 was assessed as a secondary endpoint using the time to event from first administration date to first observed (and subsequently confirmed if assessment not performed at end of study or early withdrawal visits) serum testosterone level ≥50 ng/dL or ≥1.735 nmol/L at or after Day 29, assessed using the LC-MS/MS Method and Missing Data imputed by immunoassay method Kaplan-Meier Analysis. LC-MS/MS: Liquid Chromatography-Tandem Mass Spectrometry	Day 29 through Day 183
Percentage of Subjects Demonstrating Castration With Testosterone Level <50 ng/dL at Day 95	Percentage of subjects demonstrating castration at Day 95 (3-4 days after administration of the second dose to assess the suppression of acute-on-chronic effect following the second administration) were also assessed using the LC-MS/MS method and missing data imputed by immunoassay method (at time points when LC-MS/MS data was planned to be available only) and summarised using descriptive statistics on the ITT and IC populations.	Day 95
Time to Achieve Castration (Tcast)	Time to castration (Tcast) from first administration date until first observed serum testosterone level <50 ng/dL or <1.735 nmol/L evaluated using the immunoassay method only (i.e. defined as the number of days between the injection time at Day 1 and castration achievement)	Up to Day 36
Plasma Triptorelin Levels (Cmin)	Minimal triptorelin plasma concentration at the end of each dosage interval just before the next dose injection (Cmin) for Days 92 and 183 were assessed.	At Day 92 and 183
Percentage Change in Prostate Specific Antigen (PSA) Levels From Baseline in All Subjects	Serum PSA level was presented throughout the study using descriptive statistics displaying raw values, change from Baseline and percentage change from Baseline at each visit in all subjects from the ITT population only. Additionally, the PSA level was described in subjects with elevated PSA levels (i.e. >4 ng/mL) at study entry, and the proportion of subjects with normal PSA levels (i.e. [0-4] ng/mL) at Day 183 compared to Baseline was presented.	From Day 1 (Baseline) to Day 183 (End of study)
Percentage of Subjects With Normal and Abnormal PSA Levels at Day 183 (End of Study Visit)	0-4 ng/mL (normal PSA value) >4 ng/mL (abnormal PSA levels)	At Day 183
Clinically Apparent Tumor Progression	Tumour progression was recorded according to the Investigator's clinical judgement, considering the PSA levels and any other indications of disease; the clinical confirmation might be supplemented by radiological or other investigations or scans if required. The lack of clinically apparent tumour progression was assessed at Day 92 (prior to administration of the second dose) and Day 183 (end of study visit).	Day 92 and 183
Percentage of Subjects With Adverse Events		Up to Day 183
Time to Cmax (Tmax) of Triptorelin		At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Peak Plasma Concentration Value (Cmax) of Triptorelin		At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Area Under the Concentration Versus Time Curve Between 0 and 24 Hours (AUC0-24) of Triptorelin		At 1, 2, 3, 4, 5, 6, 7, 8 and 24 hours after first dose on Day 1
Cmin of Triptorelin in Subset of 18 Subjects		At Day 92 and 183

Collaborators and Investigators

• Sponsor: Ipsen
• Investigators: Study Director: Medical Director, Uro-Oncology, Ipsen

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 24, 2012
• First Submitted That Met QC Criteria: October 24, 2012
• First Posted (Estimate): October 26, 2012

Study Record Updates

• Last Update Posted (Actual): December 9, 2019
• Last Update Submitted That Met QC Criteria: November 21, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate
• Other Study ID Numbers: 8-55-52014-200; 2012-001279-35 (EudraCT Number)