To evaluate the efficacy of triptorelin embonate 22.5 mg 6-month formulation administered subcutaneously in maintaining serum testosterone castrate levels in participants with advanced prostate cancer previously treated and castrated with a GnRH…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
- Prostatic disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• To evaluate the efficacy of triptorelin embonate 22.5 mg 6-month formulation
administered subcutaneously in maintaining serum testosterone castrate levels
in participants with advanced prostate cancer previously treated and castrated
with a GnRH analogue.
Secondary outcome
• Percentage of participants maintaining castrate levels of serum testosterone
during the study (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)
• Percentage of participants castrated at each timepoint on Day 29, Day 85, Day
141, Day 169, Day 253, Day 309 and Day 337, (castration defined as testosterone
<1.735 nmol/L (50 ng/dL)
• Percentage of participants with a serum testosterone level <0.694 nmol/L (20
ng/dL) during the study
• Percentage of participants with a serum testosterone level <0.694 nmol/L (20
ng/dL) at each timepoint on Day 29, Day 85, Day 141, Day 169, Day 253, Day 309
and Day 337
• Percentage of participants castrated, on Day 3 and Day 7 after each injection
administered on Day 1 and Day 169
(castration defined as testosterone <1.735 nmol/L (50 ng/dL))
• Percent change in PSA from baseline (prior to injection) at Day 169 and Day
337
(Percent change in PSA defined as the absolute value of difference between the
PSA values at Day 169 and Day 337 and the baseline value divided by the
baseline value)
• Incidence of TEAEs (including local tolerability) throughout the study i.e.
up to Day 337
• Change from baseline in clinical safety laboratory parameters (blood
chemistry and haematology) at Day 337
• Change from baseline in physical examination at Day 169 and Day 337
• Change from baseline in ECG at Day 337
• Change from baseline in vital signs (blood pressure and heart rate) at each
visit up to Day 337
Background summary
Prostate cancer is the second most common cancer in the male population and
thus the sixth cause of death from cancer in men over 50 in the western world
[Sung 2021]. Prostate cancer is androgen dependent, with most patients
initially responding to androgen deprivation therapy (ADT). However, after 1 to
2 years of treatment, advanced prostate cancer eventually progresses to
castration resistant prostate cancer.
Androgen receptor signalling plays an important role in the development of
prostate cancer. Gonadotropin-releasing hormone, also known as luteinizing
hormone releasing hormone (LHRH) is released in a pulsatile manner by the
hypothalamus and stimulates the pituitary to release in pulses the
gonadotropins luteinizing hormone (LH) and follicle stimulating hormone (FSH).
LH stimulates the production of testosterone by the testis; however,
approximately 5% of circulating testosterone is independently produced by the
adrenal glands. FSH plays a role in the regulation of spermatogenesis.
Since the pioneering studies of Huggins and Hodges [1941, 1941a] in the 1940's
about the role played by the testicular androgen development and progression of
prostate cancer cells, the mainstay of treatment for advanced prostate cancer
has been androgen deprivation by bilateral orchiectomy and/or oestrogen
therapy. The limitations of these therapeutic modalities led to the development
of GnRH analogues, which have made pharmacological castration the preferred
option among many patients with metastatic disease [Filicori 1994].
The therapeutic activity of the GnRH agonists is achieved via pituitary
down-regulation of their own receptors achieved by continuous and chronic
administration, providing almost complete suppression of LH and FSH secretion
leading to suppression of testicular function.
Subcutaneous injection of triptorelin 11.25 mg (3-month formulation) has been
evaluated in an open-label, single-arm study where treatment was administered
twice over a 6-month period [Lebret 2015]. Results showed subcutaneous
injection of triptorelin was well tolerated and maintained castration for up to
6 months, similarly, to results from studies with triptorelin administered
intramuscularly. Furthermore, results from a clinical study with triptorelin
embonate 22.5 mg (6-month formulation) administered twice subcutaneously over a
1-year period in participants with advanced prostate cancer who were
non-castrated, showed induction and maintenance of castration (i.e. serum
testosterone <1.735 nmol/L) in the majority of participants (82.6%) (data on
file). Subcutaneous injection of triptorelin 22.5 mg was also well tolerated,
with mild to moderate injection site AEs reported in 5.0% of participants.
Study objective
To evaluate the efficacy of triptorelin embonate 22.5 mg 6-month formulation
administered subcutaneously in maintaining serum testosterone castrate levels
in participants with advanced prostate cancer previously treated and castrated
with a GnRH analogue.
Study design
This is a phase III, multicentre, open-label, non-comparative, repeated dose
study to evaluate the efficacy and safety of triptorelin embonate 22.5 mg
6-month formulation administered subcutaneously in participants with locally
advanced and/or metastatic prostate cancer previously treated and castrated
with a GnRH analogue. Approximately 145 adult male participants will be
enrolled in the study. All enrolled participants will receive a subcutaneous
injection of triptorelin embonate 22.5 mg 6-month formulation on Day 1 and Day
169. Note: participants must receive study intervention on Day 1 in accordance
with the treatment schedule of their previously received GnRH analogue therapy.
Intervention
Triptorelin embonate 22.5 mg (6-month formulation), subcutaneous injection on
Day 1 and Day 169.
Study burden and risks
Blood samples
52-week examination (including a maximum of 4 weeks for screening)
Study procedures
Risks of the procedures
Side effects of the medication
quai Georges Gorse 65
Boulogne Billancourt 92100
FR
quai Georges Gorse 65
Boulogne Billancourt 92100
FR
Listed location countries
Age
Inclusion criteria
1. Participant is male and must be 18 years of age inclusive, at the time of
signing the informed consent.
2. 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.
3. 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).
4. Has serum testosterone levels <1.735 nmol/L (50 ng/dL) at screening.
5. Has Eastern Cooperative Oncology Group (ECOG) performance status score of 0
to 1 (see Appendix 10.4).
6. Has a life expectancy of >18 months.
7. 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.
8. Capable of giving signed informed consent as described in Appendix 10.1
which includes compliance with the requirements and restrictions listed in the
informed consent form (ICF) and in this protocol
Exclusion criteria
Medical conditions
1.Presence of another neoplastic lesion or brain metastases.
2.Metastatic hormone-sensitive prostate cancer with high tumour burden
3.Metastatic castration-resistant prostate cancer
4.Any concomitant disorder or resulting therapy that is likely to interfere
with participant compliance or with the study in the opinion of the
investigator.
Prior/concomitant therapy
5.Use of finasteride (Proscar®) or dutasteride (Avodart®/Avolve®) within the
past 6 months
6.Planned intermittent scheme of GnRH analogue
7.Use of any other therapy for prostate cancer during the study (e.g.
chemotherapy)
8.Prior hypophysectomy or adrenalectomy
Prior/concurrent clinical study experience
9.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.
Diagnostic assessments
10.Severe kidney or liver failure (creatinine >2 times the normal range,
aspartate aminotransferase and alanine aminotransferase >3 times the normal
range)
Other exclusions
11.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.
12.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
13.Known hypersensitivity to triptorelin or any of its excipients, GnRH, other
GnRH agonist/analogues.
14.Known active use of recreational drug or alcohol dependence in the opinion
of the investigator
15.Inability to give informed consent or to comply fully with the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2021-005719-29-NL |
| CCMO | NL81180.091.22 |