Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients (PEARL)
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|ClinicalTrials.gov Identifier: NCT03601143|
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : April 8, 2021
|Condition or disease||Intervention/treatment|
|Castration-resistant Prostate Cancer||Other: Blood samples prior to a new line of AR-targeted therapy|
Androgen receptor signaling inhibitors (ARSi) have become available in the past years for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and have significantly improved their survival. Despite this improvement, initial or emerging resistance to ARSi poses a major challenge in the treatment of these patients. There is therefore an urgent medical need for early detection of treatment resistance.
Liquid biopsies - blood samples containing circulating tumor cells (CTCs) and nucleic acids from the tumor - can provide information about such resistance. The investigators of this study and others have shown that liquid biopsies can be used to detect the messenger RNA (mRNA) of AR-V7, a splice variant of the androgen receptor (AR) that is insensitive to ARSi, in whole blood, and that high levels of AR-V7 mRNA in mCRPC patients are predictive to non-response to ARSi. Several liquid biopsy approaches involving different blood compartments such as CTCs, exosomes, and whole blood have been used so far to detect AR-V7. However, it is unclear which liquid biopsy approach or which combination of approaches is best to predict resistance under ARSi therapy in the clinical setting. In addition, current approaches explain only about half of resistant cases, suggesting that there are important non-AR-V7-mediated causes of resistance.
In this study, the investigators aim at determining the optimal liquid biopsy approach to detect AR-V7 and exploring novel ones for best possible prediction of resistance to ARSi. To this end, the investigators will systematically explore relevant blood compartments in a prospective cohort of mCRPC patients, quantify AR-V7 mRNA levels in each compartment, and determine the diagnostic value of compartment-specific AR-V7 mRNA levels for predicting response to subsequent ARSi therapy. The investigators will further explore the clinical relevance of AR-V7 protein subcellular localization in CTCs for prediction of ARSi resistance. In addition, novel other, AR-V7 independent mechanisms of resistance and their predictive value for proper treatment will be explored. These are based on further AR splice variants, and on neuroendocrine differentiation of prostate cancer cells.
|Study Type :||Observational|
|Estimated Enrollment :||120 participants|
|Official Title:||Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients|
|Actual Study Start Date :||March 1, 2019|
|Estimated Primary Completion Date :||November 1, 2022|
|Estimated Study Completion Date :||November 1, 2024|
- Other: Blood samples prior to a new line of AR-targeted therapy
Blood will be drawn at baseline prior to a new line of AR-targeted therapy.
- Prostate-specific antigen (PSA) decline >=50% [ Time Frame: 24 months ]The optimal liquid biopsy-based test method to predict PSA response under AR-targeted therapy will be determined.
- Clinical progression-free survival [ Time Frame: 24 months ]The optimal liquid biopsy-based test method to predict clinical progression-free survival under AR-targeted therapy will be determined.
- Overall survival [ Time Frame: 36 months ]The optimal liquid biopsy-based test method to predict overall survival under AR-targeted therapy will be determined.
Biospecimen Retention: Samples With DNA
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): NCT03601143
|Contact: Matthias M Heck, MD||+49894140 ext firstname.lastname@example.org|
|Contact: Christof Winter, MD PhD||+49894140 ext email@example.com|
|Technical University of Munich, Klinikum rechts der Isar, Department of Urology and Institute of Clinical Chemistry||Recruiting|
|Munich, Germany, 81675|
|Contact: Matthias M Heck, MD +49894140 ext 2508 firstname.lastname@example.org|
|Contact: Christof Winter, MD PhD +49894140 ext 4765 email@example.com|
|Principal Investigator:||Matthias M Heck, MD||Technische Universität München|
|Principal Investigator:||Christof Winter, MD PhD||Technische Universität München|