Study of PCUR-101 in Combination With ADT in Patients With mCRPC

A Phase I Study of PCUR-101 in Combination With Androgen Directed Therapy in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer

This is an open label, non-randomized, Phase I, dose escalation/dose expansion study in cohorts of patients with metastatic CRPC at Screening. Dose escalation uses a 3+3 design to determine the maximum tolerated dose (MTD). Once the MTD is defined, the dose expansion phase is used to define the recommended phase 2 dose.

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: PCUR-101; Drug: Dutasteride 0.5 mg; Drug: Abiraterone and Prednisone

Detailed Description

Dose Escalation Phase: Eligible patients will enter the study and start receiving daily doses of PCUR-101 during Cycle 1. Subsequent dose cohorts will receive the next higher dose of PCUR-101 according to a 3 + 3 design until the MTD is determined. Patients may remain on these treatment cycles if they do not progress or experience any dose limiting toxicities (DLTs).

Dose Expansion Phase: Once the MTD has been determined, approximately 18 patients in 3 cohorts will be enrolled for further evaluations of safety, PK, and preliminary clinical activity during successive 28-day cycles in the dose expansion phase: Expansion Cohort 1 will receive PCUR-101 at the MTD, Expansion Cohort 2 will receive PCUR-101 at one dose level lower than the MTD and dutasteride once daily, and Expansion Cohort 3 (6 patients) will receive PCUR-101 at one dose level lower than the MTD in patients about to start abiraterone (1000 mg QD) and prednisone (5 mg twice daily [BID]) as their standard of care.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • St. George Private hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Southern Oncology Clinical Research
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Nebraska Cancer Specialist

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of prostate cancer
• Demonstrates metastatic CRPC
• Castrate level of serum testosterone at screening
• Adequate hematologic, renal, and hepatic function
• ECOG status ≤1
• Life expectancy of at least 3 months
• No more than one prior course of cytotoxic chemotherapy

Exclusion Criteria:

• Pure small cell, neuroendocrine or other variant (non-adenocarcinoma) prostate cancer histology
• Visceral metastasis excluding lymph nodes
• Use of opiate analgesics for prostate cancer pain or non-cancer pain
• other investigational agents or concurrent anticancer therapy other than standard androgen deprivation therapy within 4 weeks
• History of bleeding disorder
• History of seizure disorder
• Concomitant use of warfarin
• Prior exposure to PCUR-101
• History of myocardial infarction, arterial thrombotic events, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmia
• Received wide-field external beam radiation therapy within 4 weeks
• Moderate to severe neuropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCUR-101 Dose Escalation; PCUR-101 dosed orally once per day in 28 day cycles. Patients will be enrolled into escalating dose levels during the dose escalation phase	Drug: PCUR-101; 50 mg capsules
Experimental: PCUR-101 Dose Expansion Cohort 1; PCUR-101 dosed orally once per day in 28 day cycles	Drug: PCUR-101; 50 mg capsules
Experimental: PCUR-101 Dose Expansion Cohort 2; PCUR-101 in combination with dutasteride dosed orally once per day in 28 day cycles	Drug: PCUR-101; 50 mg capsules; Drug: Dutasteride 0.5 mg; 0.5 mg capsules
Experimental: PCUR-101 Dose Expansion Cohort 3; PCUR-101 dosed orally once per day in combination with abiraterone (once per day) and prednisone (twice per day) in 28 day cycles	Drug: PCUR-101; 50 mg capsules; Drug: Abiraterone and Prednisone; 500 mg tablets Abiraterone with 5 mg Prednisone Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Dose Limiting Toxicity	Incidence of Adverse Adverse Events	over the first 28 days of dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of pharmacokinetic parameters - Tmax	time to peak concentrations of PCUR-101	over the first 28 days of dosing
Determination of pharmacokinetic parameters - Cmax	peak concentrations of PCUR-101	over the first 28 days of dosing
Determination of pharmacokinetic parameters - T1/2	time from maximum concentration PCUR-101 to a reduction of plasma concentration by 50%	over the first 28 days of dosing
Preliminary Evidence of efficacy/anti tumor activity - PSA levels	as assessed by PSA changes	through study completion, average of 12 months
Preliminary Evidence of efficacy/anti tumor activity - RECIST	as assessed by RECIST 1.1 criteria	through study completion, average of 12 months

Collaborators and Investigators

• Sponsor: Pellficure Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): November 20, 2023

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Steroid Synthesis Inhibitors; 5-alpha Reductase Inhibitors; Prednisone; Dutasteride
• Other Study ID Numbers: PCUR101-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No