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Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With mCRPC

Phase 1
Active, not recruiting
Conditions
Prostate Cancer Metastatic
Interventions
Registration Number
NCT02913196
Lead Sponsor
Weill Medical College of Cornell University
Brief Summary

This is a multi-center, Phase I study of apalutamide in combination with abiraterone acetate, docetaxel and prednisone in patients with metastatic mastrate resistant prostate cancer (mCRPC).

This study is designed to determine the dose that apalutamide can be administered safely in combination with abiraterone acetate, docetaxel and prednisone.

Detailed Description

Subjects are enrolled in up to three 3-6-subject cohorts and are administered combination (apalutamide, abiraterone acetate and docetaxel plus prednisone) according to a dose-escalation schedule. The first dose of docetaxel infusion begins on Day 1 Cycle 1. Daily oral apalutamide, abiraterone acetate plus twice-daily oral prednisone begins on Day 1 Cycle 1. Docetaxel 1-hour infusions are administered intravenously every 3 weeks (Q3W), preceded by oral dexamethasone. While a subject is receiving chemotherapy, a treatment cycle is defined as 21 days. Dose limiting toxicity (DLT) determination is based on toxicities observed within the initial 2 cycles defined as 6 weeks. DLT will be assessed before the start of the third docetaxel infusion. Once a combination dose is determined to be safe (i.e. no more than 2 of 6 subjects experience DLT), the next cohort will enroll. Subjects remain at their allocated combination dose until the maximum tolerated dose (MTD) is determined.

The primary objective is to determine a safe dose combination of apalutamide plus abiraterone acetate, docetaxel, prednisone in subjects with mCRPC.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Male
Target Recruitment
16
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
All patientsApalutamideApalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
All patientsAbiraterone acetateApalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
All patientsDocetaxelApalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
All patientsPrednisoneApalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
Primary Outcome Measures
NameTimeMethod
Number of participants with dose limiting toxicities (DLT)From the time of study drug administration till PSA progression or study completion (~36 months)

Dose limiting toxicities will be measured by using the Common Terminology Criteria for Adverse Events or CTCAE version 4.0 which uses a grading scale from 1-5.

Secondary Outcome Measures
NameTimeMethod
Change in the number of subjects with prostate-specific antigen (PSA) responseStarting after 12 weeks, at the beginning of Week 4 of combination therapy with docetaxel, apalutamide, abiraterone acetate plus prednisone until PSA progression or study completion (~36 months)
Change in PSA responseAt the start of treatment until PSA progression or study completion (~36 months)

PSA response will be captured through blood sample collection and radiographic scans

Change in the time to PSA progressionAt the start of treatment until PSA progression or study completion (~36 months)

PSA progression will be determined by protocol-specific/modified Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria

Change is radiographic progression-free survivalImages will be collected at baseline, 12 weeks and at end of study, an average of 100 months

Radiographic progression will be determined via scans metric of CT, MRI and Bone scans

Change in CellSearch circulating tumor cells (CTC) enumrationCollected at baseline, 12 weeks and at end of study, an average of 100 months

CTCs will be collected via blood sample collection

Trial Locations

Locations (2)

Weill Cornell Medical College

🇺🇸

New York, New York, United States

GU Research Network/Urology Cancer Center

🇺🇸

Omaha, Nebraska, United States

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