Efficacy of Rotations Between Abiraterone Acetate and Apalutamide in mCRPC Patients (AERA)

November 15, 2020 updated by: Aristotelis Bamias, University of Athens

A Randomized Phase II Study to Investigate the Efficacy of Rotations Between Abiraterone Acetate and Apalutamide Versus Sequential Administration in Chemo-naïve Metastatic Castration Resistant Prostate Cancer Patients

A randomized phase II study comparing the sequential use of abiraterone followed after progression by apalutamide with alternating cycles of abiraterone and apalutamide

Study Overview

Status

Withdrawn

Detailed Description

This is an open-label, randomized phase II study to investigate the feasibility of alternating cycles of treatment with abiraterone plus prednisone and apalutamide compared to sequential treatment of abiratereone plus prednisone followed by apalutamide. 7 centers in Greece will participate in the study.

The study population consists of adult patients (over 18 years old) with histologically confirmed metastatic prostate adenocarcinoma who have disease progression - as defined by PCWG2 criteria - despite androgen deprivation therapy and who have not received prior therapy for their castration resistant disease.

The purpose of the study is to determine the progression free survival, feasibility and safety profile of the experimental arm compared to standard of care.

In the experimental arm alternating treatment will consist of repeating cycles of 24 weeks of treatment consisting of 12 weeks of abiraterone acetate 1000mg orally qd and prednisone 5mg orally bid, followed by 12 weeks of apalutamide 240 mg per day. There will be no wash out period between cycles.

The comparative arm will be the standard regimen of abiraterone 1000mg orally qd plus prednisone 5mg orally bid until progression, followed thereafter by apalutamide 240mg orally qd until progression.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Signed Informed Consent Age >18 years Histologically confirmed metastatic or advanced prostate cancer adenocarcinoma that has received no treatment for the castration resistant disease and has progressed during treatment with complete androgen blockade (luteinizing hormone releasing hormone agonist or antagonist and an antiandrogen eg. Bicalutamide).

Availability of a representative formalin-fixed, paraffin-embedded tumor specimen (FFPE) that enabled definitive diagnosis of prostate cancer.

Two rising PSA levels >2ng/ml measured 1 week apart during or following the most recent prior therapy for prostate cancer (PCWG2 criteria) or radiographic evidence of disease progression in bone with or without biochemical disease progression on the basis of the PSA value.

Ongoing androgen deprivation, with serum testosterone <50ng/dl ECOG performance status 0-1 at screening Adequate hematologic and organ function within 14 days before the first study treatment (hematologic parameters must be assessed >14 days after a prior transfusion, if any) as defined by

  • Hemoglobin >9g/dl
  • Neutrophils >1500/μL
  • Platelet count >100000/μL
  • Total bilirubin <1,5xULN with the following exception:

    o Patients with known Gilbert syndrome who have serum bilirubin<3xULN

  • AST and ALT<2,5xULN with the following exception

    o Patients with bone-only metastasis may have AST<5xULN, provided that ALT <2,5xULN and total bilirubin <1,5xULN

  • Serum albumin >3g/dl
  • Serum potassium ≥3.5mmol/L
  • Serum creatinine <1,5xULN or creatinine clearance of >50ml/min based on Cockcroft-Gault equation
  • Agreement by patient and/or partner to use an effective form of contraception including surgical sterilization, reliable barrier method, birth control pills, contraceptive hormone implants or true abstinence and to continue its use for the duration of the study and for 6 months after the last dose of study treatment.

Exclusion Criteria:

  • Small cell or neuroendocrine prostate carcinoma Inability or unwillingness to swallow pills Malabsorption syndrome or other condition that would interfere with enteral absorption Congenital long QT syndrome or QTc>480msec NYHA Class II to IV heart failure or LVEF <50% or ventricular arrhythmia requiring medication Previous therapy for prostate cancer with CYP17 inhibitors including ketoconazole or investigational agents (VMT-VT-464, Orteronel etc) or novel antiandrogens (enzalutamide of OMD-208) for more than 7 days Presence of visceral metastasis History of another invasive cancer within 3 years from screening, with the exception of fully treated cancers with a remote probability of recurrence Duration of previous Androgen Deprivation Therapy <12months Active infection requiring IV antibiotics

Clinically significant cardiovascular disease including the following:

  • unstable angina,
  • myocardial infarction within 6 months from screening, or
  • cerebrovascular accident within 6 months from screening Major surgical procedure within 4 weeks prior to initiation of study treatment Treatment with an investigational agent within 4 weeks prior to initiation of study treatment Unresolved, clinical significant toxicity from prior treatment Hypersensitivity reaction to the active pharmaceutical ingredient or any of the tablet components Any medical condition that restrain the patient to comply with study and follow-up procedures Inability to comply with study and follow up procedures

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Rotational
Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 for 3 cycles, followed by apalutamide 240mg qD orally for 3 cycles. The duration of each cycle is 28 days
Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally
Other Names:
  • Zytiga
apalutamide 240mg qD orally
ACTIVE_COMPARATOR: Sequential
Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally starting on Day 1 of Cycle 1 until disease progression, followed by apalutamide 240mg qD orally until second disease progression.
Abiraterone acetate 1000mg qD and prednisone 5mg bid administered orally
Other Names:
  • Zytiga
apalutamide 240mg qD orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Radiographic progression-free survival
Time Frame: Estimated up to 24 months
time until radiographic progression as assessed by PCWG2 criteria
Estimated up to 24 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: estimated up to 36 months
time until death or lost to follow up
estimated up to 36 months
Time to cytotoxic therapy initiation
Time Frame: Estimated up to 24 months
time until the beginning of chemotherapy
Estimated up to 24 months
Time until PSA progression
Time Frame: Estimated up to 24 months
time until PSA progression as defined by PCWG2 criteria
Estimated up to 24 months
Incidence, nature and severity of AEs
Time Frame: Estimated up to 24 months
recording of all AE/SAEs
Estimated up to 24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patient reported outcomes assessed using the FACT-P and EQ-5D-5L questionnaires
Time Frame: Estimated up to 24 months
Differences in FACT-P questionnaires between treatment groups
Estimated up to 24 months
Number of Circulating Tumor Cells (CTCs) and ARv7 analysis in CTCs from peripheral blood at baseline evaluation, first and second disease progression in Arm 2 and disease progression in Arm 1 (PD1).
Time Frame: Estimated up to 24 months
Correlation of CTCs number and ARv7 expression with rPFS and OS in these patients
Estimated up to 24 months
Patient reported outcomes assessed using the EQ-5D-5L questionnaires
Time Frame: Estimated up to 24 months
Differences in EQ-5D-5L questionnaires between treatment groups
Estimated up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

January 1, 2018

Primary Completion (ANTICIPATED)

December 31, 2020

Study Completion (ANTICIPATED)

December 31, 2020

Study Registration Dates

First Submitted

May 28, 2017

First Submitted That Met QC Criteria

May 31, 2017

First Posted (ACTUAL)

June 2, 2017

Study Record Updates

Last Update Posted (ACTUAL)

November 18, 2020

Last Update Submitted That Met QC Criteria

November 15, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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