Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With mCRPC
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|ClinicalTrials.gov Identifier: NCT02913196|
Recruitment Status : Recruiting
First Posted : September 23, 2016
Last Update Posted : March 12, 2020
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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Cancer Metastatic||Drug: Apalutamide Drug: Abiraterone acetate Drug: Docetaxel Drug: Prednisone||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC)|
|Study Start Date :||December 2016|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||June 2022|
Experimental: All patients
Apalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2
Orally available, small molecule, nonsteroidal potent and selective antagonist of the androgen receptor.
Cohort 1 dose: 120 mg QD Cohort 2 dose: 240 mg QD Cohort 3 dose: 180 mg QD
Other Name: ARN-509
Drug: Abiraterone acetate
Abiraterone acetate is the prodrug of the active drug abiraterone. Once absorbed after oral administration, abiraterone acetate is rapidly converted to the active form, abiraterone.
Dose: 1000 mg QD
Other Name: Zytiga
Taxane cytotoxic chemotherapy with demonstrated survival benefit in those with advanced prostate cancer.
Dose: 75 mg/m2 Q3W
Other Name: Taxotere
Dose: 5 mg BID
Other Name: Deltasone
- Number of participants with dose limiting toxicities (DLT) [ Time Frame: 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.
- Change in the number of subjects with prostate-specific antigen (PSA) response [ Time Frame: Starting 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 response [ Time Frame: At 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 progression [ Time Frame: At 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 survival [ Time Frame: Images 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) enumration [ Time Frame: Collected at baseline, 12 weeks and at end of study, an average of 100 months ]CTCs will be collected via blood sample collection
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02913196
|Contact: GUONC Research Teamfirstname.lastname@example.org|
|United States, Nebraska|
|GU Research Network/Urology Cancer Center||Recruiting|
|Omaha, Nebraska, United States, 68130|
|Contact: Heather Mittelstedt 402-991-8468 email@example.com|
|Principal Investigator: Luke Nordquist, MD|
|United States, New York|
|Weill Cornell Medical College||Recruiting|
|New York, New York, United States, 10065|
|Contact: GUONC Research Team firstname.lastname@example.org|
|Principal Investigator: Ana M Molina, MD|
|Principal Investigator:||Scott Tagawa, MD||Weill Medical College of Cornell University|