Clinical trial NCT04677855: Study of PCUR-101 in Combination With ADT in Patients With mCRPC
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Prostate Cancer
Lead sponsor: Pellficure Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2020-12-21
Enrollment: 7
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part 1 dose escalation followed by a dose expansion
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Occurrence of Dose Limiting Toxicity
timeFrame: over the first 28 days of dosing
Secondary outcomes:
measure: Determination of pharmacokinetic parameters - Tmax
timeFrame: over the first 28 days of dosing
measure: Determination of pharmacokinetic parameters - Cmax
timeFrame: over the first 28 days of dosing
measure: Determination of pharmacokinetic parameters - T1/2
timeFrame: over the first 28 days of dosing
measure: Preliminary Evidence of efficacy/anti tumor activity - PSA levels
timeFrame: through study completion, average of 12 months
measure: Preliminary Evidence of efficacy/anti tumor activity - RECIST
timeFrame: through study completion, average of 12 months
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Omaha
country: United States
facility: Nebraska Cancer Specialist
state: Nebraska
city: Kogarah
country: Australia
facility: St. George Private Hospital
state: New South Wales
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research
state: South Australia
Study officials:
References: