Prospective Multicentre Cohort Study PROREPAIR-B (mCRPC)

Prostate Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03075735
• Other study ID #: CNIO-CP-2013-02-B
• Status: Completed
• Start date: January 15, 2013
• Est. completion date: December 15, 2018

Study information

• Verified date: February 2019
• Source: Centro Nacional de Investigaciones Oncologicas CARLOS III
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 408
• Est. completion date: December 15, 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
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).

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	42 months
Secondary	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	42 months
Secondary	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.	42 months
Secondary	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.	42 months
Secondary	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.	42 months
Secondary	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.	42 months
Secondary	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.	42 months