Comparison of Standard vs. Therapeutic Drug Monitoring-Guided Abiraterone Acetate Dosing in Patients with Metastatic Castration-Resistant Prostate Cancer

Trial ID: 2025-524440-35-00
Protocol: M25ABI
Sponsor: Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Trial statistics

science

test molecule

location_city

research site

public

country

medical_information

disease

person_search

investigator

Diseases & Conditions

Hormone-refractory prostate cancer

Objectives

The primary objective is to compare radiographic progression-free survival between patients receiving therapeutic drug monitoring guided dosing of abiraterone acetate and those receiving fixed dosing, specifically within a subgroup exhibiting a trough concentration (Cmin) below 8.4 ng/mL. This evaluation aims to determine if individualized dosing based on blood levels improves clinical outcomes in patients with metastatic castration-resistant prostate cancer. 5

Secondary objectives include the assessment of:

Overall survival, overall response rate, and time on treatment.
Prostate-specific antigen response rate, maximal response, response at 12 weeks, and time to PSA progression.
Safety, including toxicity, feasibility of monitoring, and clinical progression.
Quality of life and adherence levels for both physicians and patients.
Cost-effectiveness.

Participants

The sponsor did not provide information regarding the total number of participants. The study population consists of males aged between 18 and 64 years diagnosed with metastatic castration-resistant prostate cancer. Inclusion requires histologically or cytologically confirmed disease and the presence of measurable disease according to RECIST version 1.1. Eligible participants may be chemotherapy-naïve or have previously received one line of docetaxel-based chemotherapy during the hormone-sensitive prostate cancer or castration-resistant stages.

Plans and Procedures

This Phase IV clinical trial is designed to compare standard dosing of abiraterone acetate against dosing guided by therapeutic drug monitoring in patients with metastatic castration-resistant prostate cancer. The primary objective is to evaluate radiographic progression-free survival in a subgroup of patients who exhibit a trough concentration below 8.4 ng/mL. Secondary endpoints include safety, overall survival, prostate-specific antigen response rate, and quality of life. The study involves a screening visit to confirm eligibility based on histologically or cytologically confirmed disease and measurable disease according to RECIST criteria. Participants may be chemotherapy-naïve or have previously received docetaxel. The trial will involve regular monitoring to assess toxicity and physician adherence to dosing advice. The total duration of the study is estimated to span from May 2026 to April 2035.

Treatment

The experimental treatment consists of abiraterone acetate administered as 500 mg film-coated tablets. The prescribed dosage is 1500 mg via the oral route. The study evaluates the efficacy of standard dosing protocols compared to therapeutic drug monitoring guided dosing strategies.

Efficacy

The primary efficacy endpoint for this study is radiographic progression-free survival (PFS). This parameter is evaluated by comparing the subgroup of patients in the therapeutic drug monitoring (TDM)-guided dosing arm with a minimum concentration (Cmin) of less than 8.4 ng/mL at a specific time point during treatment against the patients in the fixed dosing arm with a Cmin below the same threshold.

Secondary efficacy and clinical outcomes include:

Clinical progression
Overall response rates (ORR)
Prostate-specific antigen (PSA) response rate
PSA response at 12 weeks
Maximal PSA response
Time to PSA progression
Overall survival (OS)
Quality of life (QoL)
Time on treatment (ToT)

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Patients with metastatic castration-resistant prostate cancer (mCRPC)
Male ≥18 years old
Histologically or cytology confirmed prostate cancer
Patients can either be chemotherapy-naïve or have received one line of docetaxelbased chemotherapy in the HSPC or CRPC stage
Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
Signed written Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures

cancel

Exclusion Criteria

Patients with metastatic hormone sensitive prostate cancer (mHSPC)
Patients who were previously treated with an androgen receptor signalling inhibitor (e.g. abiraterone, enzalutamide, darolutamide)
Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug
Consumption of agents which induce CYP3A4 (with the exception of dexamethasone) or agents with severe QT prolonging effects within 14 days prior to admission and during the study (see concomitant medication restrictions)
Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the participant in this study.
Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.