Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03075735
Recruitment Status : Completed
First Posted : March 9, 2017
Last Update Posted : February 4, 2019
Sponsor:
Collaborators:
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Instituto de Investigación Biomédica de Málaga (IBIMA).
Information provided by (Responsible Party):
Centro Nacional de Investigaciones Oncologicas CARLOS III

Brief 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.

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.


Condition or disease
Prostate Cancer

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.


Layout table for study information
Study Type : Observational [Patient Registry]
Actual Enrollment : 408 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 36 Months
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)
Actual Study Start Date : January 15, 2013
Actual Primary Completion Date : May 2018
Actual Study Completion Date : December 15, 2018

Resource links provided by the National Library of Medicine


Group/Cohort
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



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Analysis of the impact of other germline mutations in other DNA repair genes [ Time Frame: 42 months ]
    To analyze the impact of other germline mutations in other DNA repair genes on cause-specific survival from diagnosis of metastatic castration resistance

  2. Correlation between DNA repair germline mutation carrier status and survival [ Time Frame: 42 months ]
    To explore the correlation between DNA repair germline mutation carrier status and cause-specific survival following first, second, third and successive treatment lines.

  3. Correlation between DNA repair germline mutation and biochemical response [ Time Frame: 42 months ]
    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.

  4. Correlation between DNA repair germline mutation and radiographic response [ Time Frame: 42 months ]
    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.

  5. Correlation between somatic DNA repair abnormalities with cause-specific survival [ Time Frame: 42 months ]
    To explore in this cohort the correlation between somatic DNA repair abnormalities with cause-specific survival and other treatment-related outcomes.

  6. Correlation between DNA repair somatic and germline alterations with prior prostate cancer history [ Time Frame: 42 months ]
    To correlate DNA repair somatic and germline alterations with prior prostate cancer history characteristics and established risk factors.


Biospecimen Retention:   Samples With DNA
Whole blood, plasma, serum, archival FFPE and fresh tumour samples


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Recently diagnosed castration resistant prostate cancer without known mutation carrier status at study entry
Criteria

Inclusion Criteria:

  1. Provision of signed informed consent.
  2. Patients must be ≥18 years old.
  3. Histologically confirmed prostate cancer
  4. presence of metastatic disease according to Bone-, CT- and/or MRI-scan.
  5. 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.
  6. 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.
  7. ECOG performance status ≤21.
  8. Unknown mutation carrier status at the study entry.

Exclusion Criteria:

  1. 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.
  2. 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.

Information from the National Library of Medicine

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): NCT03075735


Sponsors and Collaborators
Centro Nacional de Investigaciones Oncologicas CARLOS III
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Instituto de Investigación Biomédica de Málaga (IBIMA).
Investigators
Layout table for investigator information
Principal Investigator: David Olmos, MD Centro Nacional de Investigaciones Oncologicas CARLOS III

Additional Information:

Layout table for additonal information
Responsible Party: Centro Nacional de Investigaciones Oncologicas CARLOS III
ClinicalTrials.gov Identifier: NCT03075735     History of Changes
Other Study ID Numbers: CNIO-CP-2013-02-B
First Posted: March 9, 2017    Key Record Dates
Last Update Posted: February 4, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centro Nacional de Investigaciones Oncologicas CARLOS III:
Castration-Resistant Prostate Cancer
DNA-repair
BRCA1
BRCA2
ATM
PALB2

Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases