Open-label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer

• Status: Recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Propella Therapeutics

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.