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

• ClinicalTrials.gov Identifier: NCT04729114
• Recruitment Status: Not yet recruiting
• First Posted: January 28, 2021
• Last Update Posted: March 22, 2021
• Sponsor: Propella Therapeutics
• Information provided by (Responsible Party): Propella Therapeutics

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: abiraterone decanoate	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 33 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This is a 3+3 dose escalation study design with a dose expansion phase once a Phase 2 dose is identified.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer
• Estimated Study Start Date: June 1, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; The starting dose will be 180 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection)	Drug: abiraterone decanoate; PRL-02 depot (abiraterone decanoate for intramuscular injection) is a solution formulation of abiraterone decanoate at a concentration of 180 mg/mL and will be provided as a 10 mL vial containing 990 mg of abiraterone decanoate in 5.5 mL of solution. PRL-02 will be administered as an intramuscular injection every 84 days (+3 days)
Experimental: Cohort 2; Cohort 2 dose will be 360 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection)	Drug: abiraterone decanoate; PRL-02 depot (abiraterone decanoate for intramuscular injection) is a solution formulation of abiraterone decanoate at a concentration of 180 mg/mL and will be provided as a 10 mL vial containing 990 mg of abiraterone decanoate in 5.5 mL of solution. PRL-02 will be administered as an intramuscular injection every 84 days (+3 days)
Experimental: Cohort 3; Cohort 3 dose will be 720 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection)	Drug: abiraterone decanoate; PRL-02 depot (abiraterone decanoate for intramuscular injection) is a solution formulation of abiraterone decanoate at a concentration of 180 mg/mL and will be provided as a 10 mL vial containing 990 mg of abiraterone decanoate in 5.5 mL of solution. PRL-02 will be administered as an intramuscular injection every 84 days (+3 days)
Experimental: Cohort 4; Cohort 4 dose will be 1260 mg of PRL-02 depot (abiraterone decanoate for intramuscular injection)	Drug: abiraterone decanoate; PRL-02 depot (abiraterone decanoate for intramuscular injection) is a solution formulation of abiraterone decanoate at a concentration of 180 mg/mL and will be provided as a 10 mL vial containing 990 mg of abiraterone decanoate in 5.5 mL of solution. PRL-02 will be administered as an intramuscular injection every 84 days (+3 days)
Experimental: Dose Expansion; 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.	Drug: abiraterone decanoate; PRL-02 depot (abiraterone decanoate for intramuscular injection) is a solution formulation of abiraterone decanoate at a concentration of 180 mg/mL and will be provided as a 10 mL vial containing 990 mg of abiraterone decanoate in 5.5 mL of solution. PRL-02 will be administered as an intramuscular injection every 84 days (+3 days)

Outcome Measures

Primary Outcome Measures :

1. Testosterone suppression [ Time Frame: Treatment ]
   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 :

1. Safety and tolerability [ Time Frame: Treatment ]
   Reporting of number of patients with adverse events related to study drug

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure being performed.
2. Undergone orchiectomy or ongoing gonadotropin-releasing hormone agonist or antagonist therapy for at least 3 months prior to the Screening Visit, AND a serum testosterone level <50 ng/dL but >2 ng/dL at screening.
3. An Eastern Cooperative Oncology Group Performance Status of 0 or 1.
4. Patients who have documented metastatic castration-sensitive prostate cancer or metastatic castration-resistant prostate cancer , biochemical relapse (using the Prostate Cancer Working Group definition of prostate-specific antigen progression) of prostate cancer or oligometastatic prostate cancer Positron Emission Tomography positive);

5. Adequate bone marrow reserve defined as:

   • white blood count ≥3,000/µL
   • absolute neutrophil count ≥1,500/µL
   • platelet ≥100,000/µL
   • hemoglobin ≥9 gm/dL
6. Adequate renal function defined as a serum creatinine of ≤1.5 x the upper limit of normal for the reference lab or a calculated creatinine clearance of ≥50 mL/min as determined by a validated algorithm for calculating creatinine clearance.
7. Adequate hepatic function, defined as alanine aminotransferase/ aspartate aminotransferase ≤2.5 x the upper limit of normal and total bilirubin ≤1.5 x the upper limit of normal.
8. Serum albumin of ≥3 gm/dL and serum potassium of ≥3.5 mEq/L.

Exclusion Criteria:

1. Metastatic castration-resistant prostate cancer patients with hepatic metastases; and/or is more than minimally symptomatic with a reported pain score on an 11-point (0 - 10) numeric rating scale of >3
2. Known central nervous system (CNS) metastases.
3. Other active neoplastic disease requiring concurrent anti-neoplastic treatment.
4. A history of prior myocardial infarction, stroke or transient ischemic attack, or who have uncontrolled inter-current illness, including but not limited to, ongoing or active infection, New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, poorly controlled diabetes, or psychiatric illness/social situations or substance abuse.
5. Undergone major surgery or trauma within 4 weeks of the Screening Visit.
6. History of impaired pituitary or adrenal gland function (e.g., Addison's disease, Cushing's syndrome).
7. Need for systemic glucocorticoids greater than replacement doses; the use of topical, intraocular, inhalational, intranasal or intra-articular glucocorticoids is permitted.
8. Presence of visceral metastatic disease or impending fracture due to bone metastases.

Contacts and Locations

Contacts

Contact: Tim Warneke, MS; 919-397-4782; twarneke@propellatx.com

Sponsors and Collaborators

Propella Therapeutics

Investigators

• Study Chair: Michael Kurman, MD; Propella Therapeutics

More Information

• Responsible Party: Propella Therapeutics
• ClinicalTrials.gov Identifier: NCT04729114
• Other Study ID Numbers: PRL-02-1001
• First Posted: January 28, 2021
• Last Update Posted: March 22, 2021
• Last Verified: March 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Propella Therapeutics:

Testosterone; Cancer

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases