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.

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.

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