A Study of Pharmacodynamic and Genetic Parameters of Abira-DES Study Participants (NCT02217566) - Participants With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Following Unresponsive Treatment With Diethylstilbestrol (EXPLORE)

Exploratory Evaluation of Genetic Polymorphism and Pharmacodynamic Parameters in Samples of Abira-DES Study Subjects (NCT02217566) - Subjects With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Following Unresponsive Treatment With Diethylstilbestrol.

The primary purpose of this study is to evaluate the influence of HSD3B1 (1245C) germline variant and potential pharmacodynamic markers on abiraterone activity in participants with metastatic castration-resistant prostate cancer after unresponsive use of diethylstilbestrol.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Other: Serum and plasma samples analysis

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01308901
    • Sociedade Beneficiante de Senhoras - Hospital Sirio Libanes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

The population of this study comprised of participants with metastatic castration-resistant prostate cancer with disease progression following the use of diethylstilbestrol (DES) who participated in the Abira-DES study (NCT02217566) in which they were treated with abiraterone acetate.

Description

Inclusion Criteria:

• Must have a confirmed diagnosis of prostate adenocarcinoma without neuroendocrine or small cell differentiation and was a participant in the Abira-DES study (NCT0221756), which includes: diethylstilbestrol pretreatment for castration-resistant prostate cancer with evidence of disease progression or grade 3/4 toxicity with diethylstilbestrol; metastatic disease confirmed by bone examination or metastatic lesions by computed tomography or magnetic resonance
• Abiraterone acetate therapy during the Abira-DES study (NCT0221756), and peripheral blood samples have been collected from at least of the three proposed study timepoints
• Must sign, and/or his/her legally acceptable representatives, where applicable, must sign the ICF allowing the use of clinical data and biological samples in accordance with local requirements. For deceased participants who did not provide consent prior to death, permission to research their information must meet local requirements

Exclusion Criteria:

- Having withdrawn the consent to use the samples collected during their participation in the Abira-DES study (NCT02217566)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Participants with mCRPC; Participants with metastatic castration resistant prostate cancer (mCRPC) will be evaluated for genetic polymorphism and pharmacodynamic parameters from serum and plasma samples collected during the Abira-DES study (NCT02217566). Serum and plasma samples were collected after use of diethylstilbestrol (DES) and subsequent abiraterone acetate therapy. Peripheral blood samples were collected prior to initiation of abiraterone acetate therapy, after 12 weeks of therapy, and at the time of disease progression (evaluated by prostate specific antigen [PSA] response).

Other: Serum and plasma samples analysis; This is a non-interventional study and no drug will be given as part of this study. Serum and plasma samples will be collected from the participants with metastatic castration-resistant prostate cancer to evaluate genetic polymorphism and pharmacodynamic parameters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with and Without HSD3B1 (1245C) Germline Variant'	Percentage of participants with and without HSD3B1 (1245C) germline variant will be determined to evaluate the influence of HSD3B1 (1245C) germline variant on the response to abiraterone as a predictive fact.	Up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of HSD3B1 (1245C) Germ Variant	Levels of HSD3B1 (1245C) germline variant will be determined to evaluate the response to abiraterone acetate as a predictive factor.	Up to 12 months
Levels of Metabolite Delta-(4)-Abiraterone (D4A) During the Abiraterone Acetate During Treatment Phase	Levels of metabolite D4A during the abiraterone acetate during treatment phase will be evaluated.	12 Weeks
Testosterone Levels in Participants Treated with Abiraterone Acetate	Testosterone levels of participants treated with abiraterone acetate will be evaluated by the molecular analyses.	Up to 12 months
SDHEA Levels in Participants Treated with Abiraterone Acetate	SDHEA levels of participants treated with abiraterone acetate will be evaluated by the molecular analyses.	Up to 12 months
Correlation Between HSD3B1 (1245C) Variant and Testosterone Levels	Correlation between HSD3B1 (1245C) variant and testosterone levels will be reported. The genotyping of the HSD3B1 (1245 A> C) germline variant will be performed by Sanger sequencing.	Up to 12 months
Correlation Between HSD3B1 (1245C) Variant and SDHEA Levels	Correlation between HSD3B1 (1245C) variant and SDHEA levels will be reported. The genotyping of the HSD3B1 (1245 A> C) germline variant will be performed by Sanger sequencing.	Up to 12 months
Correlation Between HSD3B1 (1245C) Variant and Clinical Response	Correlation between HSD3B1 (1245C) variant and clinical response will be performed by univariate and multivariate analyses.	Up to 12 months
Correlation Between D4A Levels with Testosterone Dosage	Testosterone ultrasensitive dosages will be performed on participant serum samples. Testosterone dosage will be performed by liquid chromatography coupled with tandem mass spectrometry.	Up to 12 months
Correlation Between D4A Levels with SDHEA Dosage	SDHEA ultrasensitive dosages will be performed on participant serum samples. Dosage will be performed by liquid chromatography coupled with tandem mass spectrometry.	Up to 12 months
Correlation Between D4A Levels with Clinical Response	Correlation between D4A levels with clinical response will be performed by univariate and multivariate analyses.	Up to 12 months

Collaborators and Investigators

• Sponsor: Janssen-Cilag Farmaceutica Ltda.

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2020
• Primary Completion (Actual): November 16, 2020
• Study Completion (Actual): November 16, 2020

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Actual): January 3, 2022
• Last Update Submitted That Met QC Criteria: December 30, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CR108736; 212082PCR0026 (Other Identifier: Janssen-Cilag Farmaceutica Ltda.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No