Castration-resistant Prostate CancerPEARLNCT03601143
Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients
An observational study of Castration-resistant Prostate Cancer, run by Technical University of Munich at 1 site in Germany.
Trial summary
This study will prospectively compare liquid-biopsy based methods for prediction of resistance under androgen-receptor signaling inhibitors. The main goal is to determine the optimal method to determine androgen-receptor variant 7 (AR-V7) status. Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Castration-resistant Prostate Cancer
- What is being tested?
- Blood samples prior to a new line of AR-targeted therapy
- How many people
- 120 participants
- Where
- 1 siteGermany
- Study dates
- 1 Mar 2019to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Study population: metastatic castration-resistant prostate cancer patients planned for a new line of therapy with androgen-receptor signaling inhibitors
Who may be able to join
- 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
Who cannot join
- Persons who are in a dependency or employment relationship with the investigator or sponsor
- Planned additional concurrent anticancer therapy
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Technical University of Munich, Klinikum rechts der Isar, Department of Urology and Institute of Clinical Chemistry
Munich, 81675
Matthias M Heck, MD, +49894140 ext. 2508, matthias.heck@tum.de
Christof Winter, MD PhD, +49894140 ext. 4765, christof.winter@tum.de
About this study
This study will prospectively compare liquid-biopsy based methods for prediction of resistance under androgen-receptor signaling inhibitors. The main goal is to determine the optimal method to determine androgen-receptor variant 7 (AR-V7) status. In addition, the investigators will explore novel other, AR-V7 independent mechanisms of resistance and their predictive value for proper treatment. These are based on further AR splice variants, and on neuroendocrine differentiation of prostate cancer cells.
Read the 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.
- Conditions
- Castration-resistant Prostate Cancer
- Being tested
- Blood samples prior to a new line of AR-targeted therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood samples prior to a new line of AR-targeted therapyOther
Blood will be drawn at baseline prior to a new line of AR-targeted therapy.
What is being measured
The primary outcome is the main question the study is designed to answer.
Prostate-specific antigen (PSA) decline >=50%
The optimal liquid biopsy-based test method to predict PSA response under AR-targeted therapy will be determined.
Measured: 24 months
Secondary outcomes (2)
Clinical progression-free survival
The optimal liquid biopsy-based test method to predict clinical progression-free survival under AR-targeted therapy will be determined.
Measured: 24 months
Overall survival
The optimal liquid biopsy-based test method to predict overall survival under AR-targeted therapy will be determined.
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2018
- Study start1 Mar 2019
- Primary completion30 Jun 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- More trials run by Technical University of MunichThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Technical University of Munich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Matthias M Heck, MD, Principal investigator, Technical University of MunichChristof Winter, MD PhD, Principal investigator, Technical University of Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03601143
- Sponsor's protocol ID
- HE 7386/1-1
- Acronym
- PEARL
- Status last verified
- Apr 2022
- First submitted
- 2 Jul 2018
- Last updated
- 20 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Seitz AK, Thoene S, Bietenbeck A, Nawroth R, Tauber R, Thalgott M, Schmid S, Secci R, Retz M, Gschwend JE, Ruland J, Winter C, Heck MM. AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide. Eur Urol. 2017 Nov;72(5):828-834. doi: 10.1016/j.eururo.2017.07.024. Epub 2017 Aug 14.
PubMed 28818355
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liquid Biopsy-based Detection of Resistance to Targeted Therapy in Prostate Cancer Patients
- ClinicalTrials.gov ID
- NCT03601143
- Acronym / sponsor ID
- PEARL / HE 7386/1-1
- Conditions
- Castration-resistant Prostate Cancer
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Technical University of MunichUniversity, hospital or other
- Study start
- 1 Mar 2019 (actual)
- Primary completion
- 30 Jun 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 26 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will prospectively compare liquid-biopsy based methods for prediction of resistance under androgen-receptor signaling inhibitors. The main goal is to determine the optimal method to determine androgen-receptor variant 7 (AR-V7) status. In addition, the investigators will explore novel other, AR-V7 independent mechanisms of resistance and their predictive value for proper treatment. These are based on further AR splice variants, and on neuroendocrine differentiation of prostate cancer cells.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- metastatic castration-resistant prostate cancer patients planned for a new line of therapy with androgen-receptor signaling inhibitors
Key inclusion criteria (8 listed)
- 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):
- Metastatic disease confirmed on computed tomography (CT) or bone scan
- Planned treatment with ARSi (androgen-receptor signaling receptors)
Key exclusion criteria (2 listed)
- Persons who are in a dependency or employment relationship with the investigator or sponsor
- Planned additional concurrent anticancer therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood samples prior to a new line of AR-targeted therapyBlood will be drawn at baseline prior to a new line of AR-targeted therapy. | Other | – |
Primary outcome
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.
2 secondary outcomes
Clinical progression-free survival
Time frame: 24 months
Overall survival
Time frame: 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2022.
- Background: PubMed 28818355Seitz AK, Thoene S, Bietenbeck A, Nawroth R, Tauber R, Thalgott M, Schmid S, Secci R, Retz M, Gschwend JE, Ruland J, Winter C, Heck MM. AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide. Eur Urol. 2017 Nov;72(5):828-834. doi: 10.1016/j.eururo.2017.07.024. Epub 2017 Aug 14.
- Individual participant dataSharing planned: No
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RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
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RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
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Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthias M Heck, MD principal investigator
Technical University of Munich
Christof Winter, MD PhD principal investigator
Technical University of Munich
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Castration-resistant Prostate Cancer, run by Technical University of Munich at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Matthias M Heck, MD (+49894140 ext. 2508, matthias.heck@tum.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prostate-specific antigen (PSA) decline >=50% (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03601143, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2022.