Description:
Eligible metastatic castration-sensitive prostate cancer (mCSPC) and metastatic
castration-resistant prostate cancer (mCRPC) patients will be enrolled in the study. Phase 1
(Dose Escalation) of the study is a 3+3 design intended to identify the recommended Phase 2
dose. Phase 2a (Dose Expansion) will confirm the safety, tolerability and pharmacodynamic
effects of the recommended Phase 2 dose. All patients will receive PRL-02 as an i.m.
injection every 84 (+ 3 days) days. In both Phases, patients will undergo scheduled periodic
assessments of serum testosterone levels. All patients may remain on study unless their serum
testosterone is >1 ng/dL on 2 sequential determinations starting on Day 21 through Day 77,
the development of unacceptable toxicity, patient withdrawal of consent, at the discretion of
the investigator or following 4 complete treatment cycles. Patients with a 2nd sequential
serum testosterone is >1 ng/dL at Day 84 will be allowed to continue in the study at the
discretion of the investigator.
Title
- Brief Title: Open-label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer
- Official Title: Open-label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID:
PRL-02-1001
- NCT ID:
NCT04729114
Conditions
Interventions
Drug | Synonyms | Arms |
---|
abiraterone decanoate | | Cohort 1 |
Purpose
Eligible metastatic castration-sensitive prostate cancer (mCSPC) and metastatic
castration-resistant prostate cancer (mCRPC) patients will be enrolled in the study. Phase 1
(Dose Escalation) of the study is a 3+3 design intended to identify the recommended Phase 2
dose. Phase 2a (Dose Expansion) will confirm the safety, tolerability and pharmacodynamic
effects of the recommended Phase 2 dose. All patients will receive PRL-02 as an i.m.
injection every 84 (+ 3 days) days. In both Phases, patients will undergo scheduled periodic
assessments of serum testosterone levels. All patients may remain on study unless their serum
testosterone is >1 ng/dL on 2 sequential determinations starting on Day 21 through Day 77,
the development of unacceptable toxicity, patient withdrawal of consent, at the discretion of
the investigator or following 4 complete treatment cycles. Patients with a 2nd sequential
serum testosterone is >1 ng/dL at Day 84 will be allowed to continue in the study at the
discretion of the investigator.
Trial Arms
Name | Type | Description | Interventions |
---|
Cohort 1 | Experimental | The starting dose will be 180 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection) | |
Cohort 2 | Experimental | Cohort 2 dose will be 360 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection) | |
Cohort 3 | Experimental | Cohort 3 dose will be 720 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection) | |
Cohort 4 | Experimental | Cohort 4 dose will be 1260 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection) | |
Dose Expansion | Experimental | The recommended Phase 2a dose will be a dose from the cohort dose escalation phase that does not exceed the maximum tolerated dose and adequately suppresses serum testosterone (i.e., to less than or equal to 1 ng/dL) over the course of treatment. More than one dose may be selected for investigation in Phase 2a of the study. | |
Eligibility Criteria
Inclusion Criteria:
1. Written informed consent obtained prior to any study-related procedure being
performed.
2. Male patients at least 18 years of age or older at time of consent.
3. Histological evidence of adenocarcinoma of the prostate.
4. Patients must have one of the following documented conditions:
- Metastatic castration sensitive prostate cancer (mCSPC);
- Castration sensitive prostate cancer (CSPC) with biochemical relapse (using the
Prostate Cancer Working Group 3 [PCWG3] definition of PSA progression) of
prostate cancer;
- Castration sensitive prostate cancer (CSPC) with oligometastatic prostate cancer
(e.g., Positron Emission Tomography (PET) positive);
- Metastatic castration resistant prostate cancer (mCRPC) (only allowed in Phase 1
at the discretion of the Investigator and after a dose cohort that demonstrates
adequate suppression of serum testosterone is determined.)
5. Undergone orchiectomy or ongoing GnRH agonist or antagonist therapy for at least 1
month prior to the Screening Visit, AND a serum testosterone level <50 ng/dL but >2
ng/dL at screening.
Exclusion Criteria:
1. Metastatic castration resistant prostate cancer (mCRPC) patients more than minimally
symptomatic or with a reported pain score on an 11-point (0 - 10) numeric rating scale
of >3 over the previous 7 days.
2. Known active central nervous system (CNS) metastases. Patients with CNS metastases
that have been treated with surgery and/or radiation therapy, who are off
pharmacologic doses of glucocorticoids, and who are neurologically stable are
eligible.
3. Clinically significant cardiac disease, defined as any of the following:
- Clinically significant cardiac arrhythmias including bradyarrhythmia and/or
subjects who require anti-arrhythmic therapy (excluding beta blockers or
digoxin). Subjects with controlled atrial fibrillation are not excluded.
- Congenital long QT syndrome
- QTcF ≥450 msec at Screening.
- History of clinically significant cardiac disease or congestive heart failure
>New York Heart Association Class II or left ventricular ejection fraction
measurement of <50% at baseline. Subjects must not have unstable angina (symptoms
at rest) or new-onset angina within the last 3 months or myocardial infarction
within the past 6 months.
- Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or
diastolic blood pressure >100 mmHg which has been confirmed by 2 successive
measurements despite optimal medical management.
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident
(including transient ischemic attacks), deep vein thrombosis, or pulmonary
embolism within the 3 months before start of study medication (except for
adequately treated catheter-related venous thrombosis occurring >1 month before
the start of study medication).
4. Prior treatment with abiraterone, orteronel or current treatment with systemic
ketoconazole or any other CYP17 inhibitor.
5. Required concomitant use of strong inducers of CYP3A4 and substrates of CYP2C8 and
CYP2D6.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Male |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Testosterone suppression |
Time Frame: | Treatment |
Safety Issue: | |
Description: | To determine a preliminary recommended Phase 2 dose of PRL-02 depot that provides adequate testosterone suppression over the course of treatment. |
Secondary Outcome Measures
Measure: | Safety and tolerability |
Time Frame: | Treatment |
Safety Issue: | |
Description: | Reporting of number of patients with adverse events related to study drug |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Propella Therapeutics |
Trial Keywords
Last Updated
July 20, 2021