Prostate CancerNCT03075735
Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)
An observational study of Prostate Cancer, run by Centro Nacional de Investigaciones Oncologicas CARLOS III.
Trial summary
PROREPAIR is a prospective multicenter observational cohort study of unselected patients with metastatic Castration Resistant Prostate Cancer (mCRPC) with unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent. Read more about this study
- Who is it for?
- Ages 18 to 99 years, men only
- Conditions the study is for
- Prostate Cancer
- How many people
- 408 participants
- Where
- No sites listed yet
- Study dates
- 15 Jan 2013to 15 Dec 2018
- How long will I take part?
- 36 Months
- 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 to 99 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: Recently diagnosed castration resistant prostate cancer without known mutation carrier status at study entry
Who may be able to join
- Provision of signed informed consent.
- Patients must be ≥18 years old.
- Histologically confirmed prostate cancer
- presence of metastatic disease according to Bone-, CT- and/or MRI-scan.
- Confirmed castration resistant prostate cancer defined as disease progression despite castrate levels of testosterone (<0.5ng/mL) and either a continuous rise in the serum prostate-specific antigen (PSA) levels, the progression of preexisting disease and /or the appearance of new metastases. Patients must be maintained on aLHRH or have underwent bilateral orchiectomy.
- Eligible patients are due to start or have started first-line treatment with any approved survival-prolonging therapy for mCRPC within a period of 6 months from study entry.
- ECOG performance status ≤21.
- Unknown mutation carrier status at the study entry.
Who cannot join
- Previous cancer diagnosis, except those patients who had a localized malignant tumour and who are five years cancer-free or those diagnosed with skin cancers (of non-melanoma type) or excised in situ carcinomas.
- Any prior medical history that according to the judgement of the investigator might interfere with the subject´s granting of informed consent or the safe execution of the procedures required in the study.
About this study
Official title: Prospective Multicentre Cohort Study of the Prevalence and Clinical Impact of Germline Deleterious Mutations in DNA Repair Genes of Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
PROREPAIR is a prospective multicenter observational cohort study of unselected patients with metastatic Castration Resistant Prostate Cancer (mCRPC) with unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent.
The study aims to evaluate the impact of aberrations in DNA-repair genes,(BRCA1, BRCA2, ATM and PALB2 and other genes) on cause-specific survival from the diagnosis of the metastatic castration resistant status and other outcomes.
Read the detailed description
This is a non-interventional study in which eligible patients are prospectively followed-up until death or the end-of-study, whichever happens first.
Patients are enrolled after mCRPC diagnosis and before or within the 6 first months of starting a first-line treatment with any approved survival-prolonging agent for mCRPC. First and subsequent treatment lines will be chosen according to the patients and their treating physicians preferences and will not be dictated by this study.
A whole blood sample for germline DNA extraction as well as any available archival prostate cancer tissue samples will be collected at baseline. Optional plasma, serum and whole blood samples will be collected at baseline and at different time points along the evolution of the disease. A sample will be collected within the last 6 months of life.
Survival and treatment outcomes including biochemical, radiological and clinical progression with standard approved agents abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223 will be prospectively collected.
Primary aim is to evaluate the prevalence and impact of DNA repair germline mutations in the BRCA1, BRCA2, ATM and PALB2 genes on cause-specific survival from mCRPC. Secondary aims will include the correlation of additional germline alterations in DNA-repair with survival and treatment outcomes; the analyses of the survival and treatment outcomes impact of somatic alterations in these genes and the role of germline and somatic defects in the clonal evolution of prostate cancer.
- Conditions
- Prostate Cancer
- Keywords
- Castration-Resistant Prostate Cancer, DNA-repair, BRCA1, BRCA2, ATM, PALB2
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Metastatic castration resistant patients | The exposition to the primary analysis risk factor (germline deleterious mutation in BRCA1, BRCA2, ATM or PALB2 gene) will be determined after inclusion. Briefly, a NGS targeted-panel based on the majority of genes included in the BROCA panel and additional DNA-repair related genes has been designed based on the available technology. The pathogenicity of germline variants will be determined according to established American College of Medical Genetics and Genomics and Association for Molecular Pathology current consensus at the time of final primary outcome analyses. Variants will also be reviewed against published literature and public databases. According to their mutation-carrier status patients will be classified as: A) Mutation Carriers in BRCA1, BRCA2, ATM and PALB2 genes; B) Mutation carriers in other genes included in the BROCA panel; C) Mutation carriers in others DNA-repair genes D)Non-carriers |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations
To assess the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations on cause-specific survival from diagnosis of metastatic castration resistance status.
Measured: 42 months
Secondary outcomes (6)
Analysis of the impact of other germline mutations in other DNA repair genes
To analyze the impact of other germline mutations in other DNA repair genes on cause-specific survival from diagnosis of metastatic castration resistance
Measured: 42 months
Correlation between DNA repair germline mutation carrier status and survival
To explore the correlation between DNA repair germline mutation carrier status and cause-specific survival following first, second, third and successive treatment lines.
Measured: 42 months
Correlation between DNA repair germline mutation and biochemical response
To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the biochemical response and time to biochemical progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.
Measured: 42 months
Correlation between DNA repair germline mutation and radiographic response
To study the correlation between BRCA1, BRCA2, ATM, PALB2 and other genes mutation carrier status and the radiographic response and time to radiographic progression following treatment with abiraterone acetate, enzalutamide, radium-223, docetaxel and/or cabazitaxel.
Measured: 42 months
Correlation between somatic DNA repair abnormalities with cause-specific survival
To explore in this cohort the correlation between somatic DNA repair abnormalities with cause-specific survival and other treatment-related outcomes.
Measured: 42 months
Correlation between DNA repair somatic and germline alterations with prior prostate cancer history
To correlate DNA repair somatic and germline alterations with prior prostate cancer history characteristics and established risk factors.
Measured: 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2017
- Study start15 Jan 2013
- Primary completionMay 2018
- Study completion15 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- 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
- 408 participants (actual)
- Target duration
- 36 Months
Sponsor and investigators
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS III
- Sponsor type
- University, hospital or other
- Collaborators
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud, Instituto de Investigacion Biomedica de Malaga
- Responsible party
- Sponsor
- Investigators
- David Olmos, MD, Principal investigator, Centro Nacional de Investigaciones Oncologicas CARLOS III
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03075735
- Sponsor's protocol ID
- CNIO-CP-2013-02-B
- Status last verified
- Feb 2019
- First submitted
- 6 Mar 2017
- Last updated
- 4 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Multicentre Cohort Study of the Prevalence and Clinical Impact of Germline Deleterious Mutations in DNA Repair Genes of Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT03075735
- Acronym / sponsor ID
- CNIO-CP-2013-02-B
- Conditions
- Prostate Cancer
- Keywords
- Castration-Resistant Prostate Cancer, DNA-repair, BRCA1, BRCA2, ATM, PALB2
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 408 participants (actual)
- Lead sponsor
- Centro Nacional de Investigaciones Oncologicas CARLOS IIIUniversity, hospital or other
- Collaborators
- Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud, Instituto de Investigacion Biomedica de Malaga
- Study start
- 15 Jan 2013 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- 15 Dec 2018 (actual)
- First posted
- 9 Mar 2017 (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.
PROREPAIR is a prospective multicenter observational cohort study of unselected patients with metastatic Castration Resistant Prostate Cancer (mCRPC) with unknown germline mutational status at study entry and who are candidates to start 1st line treatment with any approved survival-prolonging agent.
The study aims to evaluate the impact of aberrations in DNA-repair genes,(BRCA1, BRCA2, ATM and PALB2 and other genes) on cause-specific survival from the diagnosis of the metastatic castration resistant status and other outcomes.
Detailed description
This is a non-interventional study in which eligible patients are prospectively followed-up until death or the end-of-study, whichever happens first.
Patients are enrolled after mCRPC diagnosis and before or within the 6 first months of starting a first-line treatment with any approved survival-prolonging agent for mCRPC. First and subsequent treatment lines will be chosen according to the patients and their treating physicians preferences and will not be dictated by this study.
A whole blood sample for germline DNA extraction as well as any available archival prostate cancer tissue samples will be collected at baseline. Optional plasma, serum and whole blood samples will be collected at baseline and at different time points along the evolution of the disease. A sample will be collected within the last 6 months of life.
Survival and treatment outcomes including biochemical, radiological and clinical progression with standard approved agents abiraterone, enzalutamide, docetaxel, cabazitaxel and radium-223 will be prospectively collected.
Primary aim is to evaluate the prevalence and impact of DNA repair germline mutations in the BRCA1, BRCA2, ATM and PALB2 genes on cause-specific survival from mCRPC. Secondary aims will include the correlation of additional germline alterations in DNA-repair with survival and treatment outcomes; the analyses of the survival and treatment outcomes impact of somatic alterations in these genes and the role of germline and somatic defects in the clonal evolution of prostate cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 36 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Metastatic castration resistant patients | – | –The exposition to the primary analysis risk factor (germline deleterious mutation in BRCA1, BRCA2, ATM or PALB2 gene) will be determined after inclusion. Briefly, a NGS targeted-panel based on the majority of genes included in the BROCA panel and additional DNA-repair related genes has been designed based on the available technology. The pathogenicity of germline variants will be determined according to established American College of Medical Genetics and Genomics and Association for Molecular Pathology current consensus at the time of final primary outcome analyses. Variants will also be reviewed against published literature and public databases. According to their mutation-carrier status patients will be classified as: A) Mutation Carriers in BRCA1, BRCA2, ATM and PALB2 genes; B) Mutation carriers in other genes included in the BROCA panel; C) Mutation carriers in others DNA-repair genes D)Non-carriers |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Recently diagnosed castration resistant prostate cancer without known mutation carrier status at study entry
Key inclusion criteria (8 listed)
- Provision of signed informed consent.
- Patients must be ≥18 years old.
- Histologically confirmed prostate cancer
- presence of metastatic disease according to Bone-, CT- and/or MRI-scan.
- Confirmed castration resistant prostate cancer defined as disease progression despite castrate levels of testosterone (<0.5ng/mL) and either a continuous rise in the serum prostate-specific antigen (PSA) levels, the progression of preexisting disease and /or the appearance of new metastases. Patients must be maintained on aLHRH or have underwent bilateral orchiectomy.
Key exclusion criteria (2 listed)
- Previous cancer diagnosis, except those patients who had a localized malignant tumour and who are five years cancer-free or those diagnosed with skin cancers (of non-melanoma type) or excised in situ carcinomas.
- Any prior medical history that according to the judgement of the investigator might interfere with the subject´s granting of informed consent or the safe execution of the procedures required in the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Assessment of the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations
Time frame: 42 months
To assess the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations on cause-specific survival from diagnosis of metastatic castration resistance status.
6 secondary outcomes
Analysis of the impact of other germline mutations in other DNA repair genes
Time frame: 42 months
Correlation between DNA repair germline mutation carrier status and survival
Time frame: 42 months
Correlation between DNA repair germline mutation and biochemical response
Time frame: 42 months
Correlation between DNA repair germline mutation and radiographic response
Time frame: 42 months
Correlation between somatic DNA repair abnormalities with cause-specific survival
Time frame: 42 months
Correlation between DNA repair somatic and germline alterations with prior prostate cancer history
Time frame: 42 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2019.
- Individual participant dataSharing planned: No
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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.
David Olmos, MD principal investigator
Centro Nacional de Investigaciones Oncologicas CARLOS III
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer, run by Centro Nacional de Investigaciones Oncologicas CARLOS III.
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: finished, as of the sponsor's last update on 4 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the impact of BRCA1, BRCA2, ATM, PALB2 germline mutations (time frame: 42 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Feb 2019.