Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)

NCT ID: NCT03075735

Last Updated: 2019-02-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 408 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-15
• Study Completion Date: 2018-12-15

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.

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

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

No interventions assigned to this group

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

OTHER

Sponsor Role: collaborator

Instituto de Investigacion Biomedica de Malaga

OTHER

Sponsor Role: collaborator

Centro Nacional de Investigaciones Oncologicas CARLOS III

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Olmos, MD

Role: PRINCIPAL_INVESTIGATOR

Centro Nacional de Investigaciones Oncologicas CARLOS III

Other Identifiers

CNIO-CP-2013-02-B

Identifier Type: -

Identifier Source: org_study_id