E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced or metastatic prostate cancer |
|
E.1.1.1 | Medical condition in easily understood language |
For the treatment of cancer that has spread to area just outside of the prostate gland and for treatment of cancer that has also spread to other parts of the body |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10060862 |
E.1.2 | Term | Prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To confirm the efficacy of triptorelin pamoate (11.25 mg)prolonged
release (PR) formulation by inducing castration (defined as serum
testosterone level of <50 ng/dL or <1.735 nmol/L) at Day 29 and
maintaining castration at Day 183 (after receiving two subcutaneous (s.c.) administrations of triptorelin pamoate, 3 months apart). |
|
E.2.2 | Secondary objectives of the trial |
•To assess the proportion of patients demonstrating castration
at Day 92 (before administration of the second dose)
• To demonstrate the ability of triptorelin to suppress the
acute-on-chronic effect following administration of the second dose, by assessing the proportion of patients castrated, 3-4 days after the second injection (Day 95)
• To assess time to castration
• To assess the residual triptorelin levels in all patients at
Days 92 and 183 (i.e. at 13 weeks following each s.c. administration)
• To assess the effect of triptorelin on prostate specific antigen
(PSA) levels
• To demonstrate the safety and the local tolerability of the
s.c. administration
• To determine the pharmacokinetic (PK) profile of triptorelin
administered s.c. as a 3 month (M) injection in a subset of
15 patients.
Exploratory Objective:
• To determine proportion of patients with a serum testosterone level of <20 ng/dL and the characteristics and
stability of such a reduction. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
. Histologically proven locally advanced or metastatic prostate
cancer who are suitable for androgen deprivation therapy
2. Male aged ≥18 years old
3. Screening testosterone level of >125 ng/dL
4. Life expectancy of greater than 12 months in the judgement
of the Investigator
5. Eastern Cooperative Oncology Group (ECOG) performance
status of 0-1
6. Willing to give signed informed consent freely
7. Able to adhere to the study visit schedule and other protocol
requirements. |
|
E.4 | Principal exclusion criteria |
1. Prior hormonal therapy for prostate cancer
2. Prior surgery or radiotherapy of prostate cancer with curative
intent unless disease is verified by a rising 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
3. Presence or history of any other malignancy except for
non-melanoma skin cancer adequately treated at least 2 years
before study entry
4. Painful local bone lesions or spinal lesions which may lead
to compression
5. 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
6. 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
7. Abnormal haematological, hepatic or renal functions:
• Haemoglobin <9 g/dL, absolute neutrophil count ≤1.5 x 109/L or platelets ≤100 x 109/L
• Serum creatinine ≥1.5 times the upper limit of normal (ULN)
• Aspartate aminotransferase or alanine aminotransferase >2.5 times the ULN
8. Known hypersensitivity to the study treatment, to any of its
excipients
9. Known active use of recreational drug or alcohol dependence
in the opinion of the Investigator
10. 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
11. Use of systemic corticosteroids (inhaled corticosteroids and
topical application of corticosteroids are permitted)
12. Aged ≥90 years for the main study and ≥80 years for those
included in the PK population
13. 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
14. Any skin or other condition that may preclude s.c. injection
administration
15. Known brain or epidural metastases. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
•The proportion of patients castrated
• The proportion of patients with castration maintained |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
•The proportion of patients castrated - Day 29
• The proportion of patients with castration maintained - Day 183 |
|
E.5.2 | Secondary end point(s) |
• The proportion of patients demonstrating castration at Day 92
• To assess the probability of testosterone <50 ng/dL from
Day 29 through Day 183
• The proportion of patients demonstrating castration at Day 95
• Determination of the time to castration (Tcast)
• Plasma triptorelin levels in all patients
• Percent change in PSA levels from Baseline in all patients and
additionally in patients with elevated PSA levels
• Proportion of patients with normal PSA levels
• Lack of clinically apparent tumour progression |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The proportion of patients demonstrating castration at Day 92
(before administration of the second dose)
• The proportion of patients demonstrating castration at Day 95
(3-4 days after administration of the second dose)
• Determination of the time to castration (Tcast)
• Plasma triptorelin levels at Days 92 and 183 in all patients
• Percent change in PSA levels from Baseline in all patients and
additionally in patients with elevated PSA levels at study entry
• Proportion of patients with normal PSA levels at Day 183 (End
of Study Visit) compared to Baseline
• Lack of clinically apparent tumour progression assessed at
Day 92 (prior to administration of second dose) and Day 183
(End of Study Visit). |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |