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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: PCUR-101
* Drug: Dutasteride 0.5 mg
* Drug: Abiraterone and Prednisone


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part 1 dose escalation followed by a dose expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PCUR-101 Dose Escalation<br>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<br>* 50 mg capsules<br>|
| Experimental: PCUR-101 Dose Expansion Cohort 1<br>PCUR-101 dosed orally once per day in 28 day cycles | Drug: PCUR-101<br>* 50 mg capsules<br>|
| Experimental: PCUR-101 Dose Expansion Cohort 2<br>PCUR-101 in combination with dutasteride dosed orally once per day in 28 day cycles | Drug: PCUR-101<br>* 50 mg capsules<br>Drug: Dutasteride 0.5 mg<br>* 0.5 mg capsules<br>|
| Experimental: PCUR-101 Dose Expansion Cohort 3<br>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<br>* 50 mg capsules<br>Drug: Abiraterone and Prednisone<br>* 500 mg tablets Abiraterone with 5 mg Prednisone Tablets<br>|

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 |