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

Astellas

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: mCSPC; mCRPC; Prostate Cancer

Treatments: Drug: docetaxel infusion; Drug: PRL-02 injection; Drug: dexamethasone; Drug: prednisone

Study type: Interventional

Funder types: Industry

Identifiers

NCT04729114

PRL-02-1001

Details and patient eligibility

About

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

Full description

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.

Enrollment: 100 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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100 participants in 10 patient groups

Cohort 1

Experimental group

Description:

180 mg PRL-02 + dexamethasone or prednisone

Treatment:

Drug: prednisone

Drug: dexamethasone

Drug: PRL-02 injection

Cohort 2

Experimental group

Description:

360 mg PRL-02 + dexamethasone or prednisone

Treatment:

Drug: prednisone

Drug: dexamethasone

Drug: PRL-02 injection

Cohort 3

Experimental group

Description:

720 mg PRL-02 + dexamethasone or prednisone

Treatment:

Drug: prednisone

Drug: dexamethasone

Drug: PRL-02 injection

Cohort 4

Experimental group

Description:

1260 mg PRL-02 + dexamethasone or prednisone

Treatment:

Drug: prednisone

Drug: dexamethasone

Drug: PRL-02 injection

Cohort 5

Experimental group

Description:

1800 mg PRL-02 + dexamethasone or prednisone

Treatment:

Drug: prednisone

Drug: dexamethasone

Drug: PRL-02 injection

Phase 1 Expansion Group D

Experimental group

Description:

Prior abiraterone

Treatment:

Drug: dexamethasone

Drug: PRL-02 injection

Phase 1 Expansion Group E

Experimental group

Description:

Prior enzalutamide, apalutamide and/or darolutamide

Treatment:

Drug: dexamethasone

Drug: PRL-02 injection

Phase 2a Dose Expansion Group F1

Experimental group

Description:

Dosing at recommended Phase 2 dose (RP2D); high volume mCSPC

Treatment:

Drug: dexamethasone

Drug: PRL-02 injection

Drug: docetaxel infusion

Phase 2a Dose Expansion Group F2

Experimental group

Description:

Dosing at RP2D; low volume mCSPC

Treatment:

Drug: dexamethasone

Drug: PRL-02 injection

Phase 2a Dose Expansion Group G

Experimental group

Description:

Dosing at RP2D; mCRPC

Treatment:

Drug: dexamethasone

Drug: PRL-02 injection