Prostate Cancer
Conditions
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.
Interventions
DRUGPCUR-101
50 mg capsules
0.5 mg capsules
DRUGAbiraterone and Prednisone
500 mg tablets Abiraterone with 5 mg Prednisone Tablets
Sponsors
Pellficure Pharmaceuticals, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 dose escalation followed by a dose expansion
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Dose Limiting Toxicity | over the first 28 days of dosing | Incidence of Adverse Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of pharmacokinetic parameters - Tmax | over the first 28 days of dosing | time to peak concentrations of PCUR-101 |
| Determination of pharmacokinetic parameters - Cmax | over the first 28 days of dosing | peak concentrations of PCUR-101 |
| Determination of pharmacokinetic parameters - T1/2 | over the first 28 days of dosing | time from maximum concentration PCUR-101 to a reduction of plasma concentration by 50% |
| Preliminary Evidence of efficacy/anti tumor activity - PSA levels | through study completion, average of 12 months | as assessed by PSA changes |
| Preliminary Evidence of efficacy/anti tumor activity - RECIST | through study completion, average of 12 months | as assessed by RECIST 1.1 criteria |
Countries
Australia, United States
Outcome results
None listed