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JOURNAL ONKOLOGIE – STUDIE
PEARL

Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients

Rekrutierend

NCT-Nummer:
NCT03601143

Studienbeginn:
März 2019

Letztes Update:
20.10.2022

Wirkstoff:
-

Indikation (Clinical Trials):
Prostatic Neoplasms

Geschlecht:
Männer

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Technical University of Munich

Collaborator:
-

Studienleiter

Matthias M Heck, MD
Principal Investigator
Technical University of Munich
Christof Winter, MD PhD
Principal Investigator
Technical University of Munich

Kontakt

Studienlocations
(1 von 1)

Technical University of Munich, Klinikum rechts der Isar, Department of Urology and Institute of Clinical Chemistry
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Matthias M Heck, MD
Phone: +49894140
Phone (ext.): 2508
E-Mail: matthias.heck@tum.de

Christof Winter, MD PhD
Phone: +49894140
Phone (ext.): 4765
E-Mail: christof.winter@tum.de
» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Histologically confirmed prostate adenocarcinoma

- Castrate serum testosterone <50ng/ml or <1.7nmol/l under continued

androgen-deprivation therapy or surgical castration

- Progressive disease at study entry in accordance with Prostate Cancer Working Group 3

criteria (PCWG3):

- Biochemical progression: Three consecutive rises in PSA at least one week apart

resulting in two 50% increases over the nadir, and a PSA >1.0 ng/ml as minimal

starting value, or

- Radiologic progression: either two or more new bone lesions on bone scan or a new

soft tissue lesion using RECIST (Response evaluation criteria in solid tumors).

- Metastatic disease confirmed on computed tomography (CT) or bone scan

- Planned treatment with ARSi (androgen-receptor signaling receptors)

- Written informed consent of the patient

Exclusion Criteria:

- Persons who are in a dependency or employment relationship with the investigator or

sponsor

- Planned additional concurrent anticancer therapy

Studien-Rationale

Primary outcome:

1. 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.



Secondary outcome:

1. 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.

2. Overall survival (Time Frame - 36 months):
The optimal liquid biopsy-based test method to predict overall survival under AR-targeted therapy will be determined.

Geprüfte Regime

  • 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.

Quelle: ClinicalTrials.gov


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