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

NCT02913196 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 1509016578
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Prostate Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities (DLT)

  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.

  From the time of study drug administration till PSA progression or study completion (~36 months)

Secondary Outcomes (5)

• Change in the number of subjects with prostate-specific antigen (PSA) response

  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

  At the start of treatment until PSA progression or study completion (~36 months)

• Change in the time to PSA progression

  At the start of treatment until PSA progression or study completion (~36 months)

• Change is radiographic progression-free survival

  Images will be collected at baseline, 12 weeks and at end of study, an average of 100 months

• Change in CellSearch circulating tumor cells (CTC) enumration

  Collected at baseline, 12 weeks and at end of study, an average of 100 months

Study Arms (1)

All patients

EXPERIMENTAL

Apalutamide, 120 mg (cohort 1), 240 mg (cohort 2), 180 mg (cohort 3) Abiraterone Acetate 1000mg Prednisone 10mg Docetaxel 75 mg/m2

Drug: Apalutamide; Drug: Abiraterone acetate; Drug: Docetaxel; Drug: Prednisone

Interventions

Apalutamide DRUG

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

Also known as: ARN-509

All patients

Abiraterone acetate DRUG

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

Also known as: Zytiga

All patients

Docetaxel DRUG

Taxane cytotoxic chemotherapy with demonstrated survival benefit in those with advanced prostate cancer. Dose: 75 mg/m2 Q3W

Also known as: Taxotere

All patients

Prednisone DRUG

Dose: 5 mg BID

Also known as: Deltasone

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of prostate
• Documented progressive metastatic CRPC based on at least one of the following criteria:
• PSA progression according to Prostate Cancer Working Group 3 (PCWG3) criteria
• Objective radiographic progression in soft tissue, according to modified Response Evaluation Criteria In Solid Tumors (RECIST) or bone scans
• ECOG performance status of 0-2
• Have serum testosterone \< 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone orchiectomy
• Age \>18 years
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count \>1,500/cells/mm3
• Hemoglobin ≥ 9 g/dL
• Platelet count \>100,000 x 109/microliter
• Serum creatinine \<1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min/1.73 m2 by Cockcroft-Gault
• Serum albumin ≥3.2 g/dL
• Serum potassium ≥3.5 mmol/L
• Patients must be able to take oral medication without crushing, dissolving or chewing tablets

You may not qualify if:

• Liver Function
• If total bilirubin is \>1.5 x ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is \>1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) or
• Alanine (ALT) or aspartate (AST) aminotransferase \>1.5xULN (or \>5xULN for subject with liver metastasis) concomitant with alkaline phosphatase \>2.5xULN (or \>5xULN for subjects with bone or liver metastases) or
• Alanine (ALT or aspartate (AST) aminotransferase \>2.5xULN (or \>5xULN for subjects with liver metastasis
• Use of investigational drugs (including vaccines) or implantation of invasive medical device ≤4 weeks or \<5 half-lives of Cycle 1, Day 1 or current enrollment in investigational drug or device study
• Prior exposure to apalutamide. Prior exposure to abiraterone acetate and/or other CYP17 inhibitors, enzalutamide is allowed (but not preferred) only during the dose escalation period
• Prior chemotherapy for advanced prostate cancer. Prior chemotherapy for any other disease within 3 years
• Prior systemic beta-emitting bone-seeking radioisotopes (i.e. strontium-90)
• Pre-existing neuropathy ≥Grade 2
• Systemic azole treatment (e.g. Fluconazole, itracanozole) ≤2 weeks of Cycle 1 Day 1
• Use of potent inducers or inhibitors of CYP3A4 activity ≤2 weeks prior to Day 1 Cycle 1
• History of adrenal insufficiency or hyperaldosteronism
• Active or symptomatic viral hepatitis
• Chronic liver disease
• Brain metastases or leptomeningeal disease

Sponsors & Collaborators

• Janssen Scientific Affairs, LLC: collaborator
• Weill Medical College of Cornell University: lead

Study Sites (2)

GU Research Network/Urology Cancer Center

Omaha, Nebraska, 68130, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Interventions

apalutamide; Abiraterone Acetate; Docetaxel; Prednisone

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Ana Molina, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 23, 2016
• Study Start: December 30, 2016
• Primary Completion: June 30, 2021
• Study Completion: October 15, 2025
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)