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

Study Overview
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Brief Summary
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A Phase 1/2a, open-label, multicenter study of intramuscular (i.m.) PRL-02 depot in participants with advanced prostate cancer.

Detailed Description
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Phase 1/2a, open-label, multicenter study of intramuscular (i.m.) PRL-02 depot in participants with castration-sensitive prostate cancer (CSPC) and metastatic castration-resistant prostate cancer (mCRPC). In Phase 1 (Dose Escalation), participants will receive escalating doses of i.m. PRL-02 in 84-day treatment cycles combined with daily oral steroid. In Phase 2a (Dose Expansion), participants with metastatic castration-sensitive prostate cancer (mCSPC) and mCRPC will receive i.m. PRL-02 at one or more recommended Phase 2 doses (RP2Ds) selected from Phase 1 in 84-day treatment cycles in combination with dexamethasone and docetaxel (Group F1) or in combination with dexamethasone (Groups F2, G). In both phases, participants will undergo scheduled periodic assessments of prostate specific antigen (PSA), testosterone and progesterone levels in the blood.

Official Title
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Phase 1/2a, Open-Label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer

Conditions
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Prostate Cancer, mCRPC, mCSPC

Intervention / Treatment
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* Drug: PRL-02 injection
* Drug: prednisone
* Drug: dexamethasone
* Drug: docetaxel infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological evidence of adenocarcinoma of the prostate, including metastatic castration sensitive prostate cancer (mCSPC); castration sensitive prostate cancer (CSPC); castration sensitive prostate cancer (CSPC); metastatic castration resistant prostate cancer (mCRPC) Undergone bilateral orchiectomy or ongoing GnRH agonist or antagonist therapy for at least 6 weeks prior to the first dose of study drug which must be continued throughout the study Eastern Cooperative Oncology Group (ECOG) of 0 or 1 For Phase1 expansion Groups D & E only, received prior darolutamide, apalutamide, abiraterone or enzalutamide and have documented evidence of progression Exclusion Criteria: Known active central nervous system (CNS) metastases, except those who have been treated with surgery and/or radiation therapy, who are off pharmacologic doses of glucocorticoids, and who are neurologically stable. Known additional malignancy beyond prostate cancer that required active treatment with the exception of: adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ carcinoma of any type; adequately treated Stage I cancer from which the patient is currently in remission and has been in remission for ≥2 years; any other cancer from which the patient has been disease-free for ≥5 years Clinically significant cardiac disease Received chemotherapy within 2 weeks or 5 half-lives of first dose of study drug Current treatment with enzalutamide, flutamide, nilutamide, bicalutamide, or any other androgen receptor (AR) blocking agents. Patients who have received anti-androgens or AR blocking agents must have discontinued bicalutamide ≥6 weeks and other antiandrogens ≥4 weeks prior to the first dose of PRL-02. Prior treatment with estrogens within 12 weeks of the first dose of study drug Need for systemic glucocorticoids greater than replacement doses; the use of topical, intraocular, inhalational, intranasal, or intra-articular glucocorticoids is permitted. Required concomitant use of strong inducers of CYP3A4. Known hypersensitivity to PRL-02, abiraterone, abiraterone decanoate, prednisone, or dexamethasone or any of their excipients or components. Hemoglobin A1c (HbA1c) >10% in patients previously diagnosed with diabetes mellitus. HbA1c >8% in patients whose diabetes mellitus is previously undiagnosed. (Excluded patients may be rescreened after referral and evidence of improved control of their condition). Body mass index > 40 kg/m^2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>180 mg PRL-02 + dexamethasone or prednisone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: prednisone<br>* 5 mg once daily or twice daily<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Cohort 2<br>360 mg PRL-02 + dexamethasone or prednisone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: prednisone<br>* 5 mg once daily or twice daily<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Cohort 3<br>720 mg PRL-02 + dexamethasone or prednisone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: prednisone<br>* 5 mg once daily or twice daily<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Cohort 4<br>1260 mg PRL-02 + dexamethasone or prednisone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: prednisone<br>* 5 mg once daily or twice daily<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Cohort 5<br>1800 mg PRL-02 + dexamethasone or prednisone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: prednisone<br>* 5 mg once daily or twice daily<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Phase 1 Expansion Group D<br>Prior abiraterone | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Phase 1 Expansion Group E<br>Prior enzalutamide, apalutamide and/or darolutamide | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Phase 2a Dose Expansion Group F1<br>Dosing at recommended Phase 2 dose (RP2D); high volume mCSPC | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>Drug: docetaxel infusion<br>* docetaxel administered via intravenous infusion<br>|
| Experimental: Phase 2a Dose Expansion Group F2<br>Dosing at RP2D; low volume mCSPC | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|
| Experimental: Phase 2a Dose Expansion Group G<br>Dosing at RP2D; mCRPC | Drug: PRL-02 injection<br>* abiraterone decanoate for intramuscular injection<br>Drug: dexamethasone<br>* 0.5 mg administered once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (adverse events) | Determine the incidence rates for adverse events using NCI CTCAE v5.0 grading through study completion, an average of 1 year | Treatment | 
| Determination of recommended Phase 2 dose (RP2D) | Select RP2D of PRL-02 depot by evaluation of safety parameters up to 84 days | Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate pharmacokinetics (PK) profile of PRL-02 | Determination of PK profiles of PRL-02 up to 84 days | Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testosterone, Testosterone suppression, metastatic castrate sensitive prostate cancer, metastatic castrate resistant prostate cancer, metastatic disease, prostate cancer, mCSPC, mCRPC, abiraterone, abiraterone decanoate, abiraterone acetate, Phase 1/2a, Propella