International Breast Cancer Biomarker,Standard of Care and Real World Outcomes Study

NCT ID: NCT03078036

Last Updated: 2020-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

873 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-13

Study Completion Date

2019-05-20

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

BREAKOUT -International Breast Cancer Biomarker, Standard of Care and Real World Outcomes Study BREAKOUT is a prospective cross-sectional cohort study of human epidermal growth factor receptor 2 negative metastatic breast cancer patients who have started 1st line systemic cytotoxic chemotherapy. The study will estimate the prevalence of germline breast cancer susceptibility gene in an otherwise unselected population, describe the treatments administered and estimate the associated clinical outcomes of overall survival and progression-free survival amongst mutation carriers within the context of a low poly ADP ribose polymerase inhibitor treatment setting. Other exploratory analyses may be undertaken to describe somatic breast cancer susceptibility gene and other homologous recombination repair gene mutations.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Background/Rationale: Within the setting of metastatic human epidermal growth factor receptor 2 negative (HER2-ve) breast cancer limited epidemiological data exist on the prevalence of pathogenic mutations of breast cancer susceptibility gene (BRCA) and other homologous recombination repair (HRR) genes. There are also limited data on the treatments and clinical outcomes of patients with such germline and somatic genetic profiles, particularly within this setting. This epidemiologic study will estimate the prevalence of germline breast susceptibility gene (gBRCA) mutations among metastatic HER2-ve patients who have commenced 1st line systemic cytotoxic chemotherapy and, at that time, are considered to have exhausted hormone therapy options (if hormone receptor positive \[HR+ve\]), per investigator's opinion. Among those patients with a gBRCA gene mutation, treatment patterns and clinical outcomes will be described. This study may also explore the prevalence of somatic BRCA (sBRCA) mutations and other HRR gene mutations among metastatic HER2-ve patients who have commenced 1st line systemic cytotoxic chemotherapy. The treatment patterns and clinical outcomes may be described among those patients with a sBRCA gene mutation and those with other HRR gene mutations.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Breast Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

OTHER

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Observation

Human epidermal growth factor receptor 2 negative metastic breast cancer patients who have started 1st line systemic cytotoxic chemotheraphy and are considered to have exhausted hormone therapy options (if HR+ve), per investigator's opinion.

Germline BRCA Test (blood)

Intervention Type GENETIC

If unavailable from the patient medical records, gBRCA gene mutation status will be tested as aligned to local clinical practice using a blood sample obtained preferably during routine clinical practice. (Note: Blood samples may be shipped to a central laboratory for testing and storage, based on local regulations for shipment of blood samples.)

FoundationOne Dx Genomic Profile (archival Tumour Specimen)

Intervention Type GENETIC

Archival tumour specimen will be requested from all patients in the informed consent, but is not required for study enrolment (optional consent). Where sufficient archival tumour specimen is available and patients have consented to tumour specimen testing, FoundationOne Dx genomic profiling may take place as follows:

* Tumour Specimen: Acceptable samples include formalin-fixed, paraffin embedded (FFPE) tissue (preferred) or FFPE specimens, including core needle biopsies, fine-needle aspirates and effusion cytologies.
* Tumour Testing (optional): archival tumour specimens, where available, will be tested for mutations in HRR genes including BRCA1 and BRCA2 and other genomic alterations using the FoundationOne Dx genomic profile.

Follow-up

Intervention Type OTHER

Patients who test positive for a gBRCA gene mutation, and/or sBRCA or other HRR gene mutations (optional testing), will be followed prospectively for assessment of treatment patterns and associated clinical outcomes up to 30-months.

\- Patients who test negative for gBRCA gene mutations, sBRCA and other HRR gene mutations, no further data will be collected post baseline. Patients presenting other genomic alterations that are identified by the FoundationOne Dx genomic profile will not continue beyond baseline as part of this study.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Germline BRCA Test (blood)

If unavailable from the patient medical records, gBRCA gene mutation status will be tested as aligned to local clinical practice using a blood sample obtained preferably during routine clinical practice. (Note: Blood samples may be shipped to a central laboratory for testing and storage, based on local regulations for shipment of blood samples.)

Intervention Type GENETIC

FoundationOne Dx Genomic Profile (archival Tumour Specimen)

Archival tumour specimen will be requested from all patients in the informed consent, but is not required for study enrolment (optional consent). Where sufficient archival tumour specimen is available and patients have consented to tumour specimen testing, FoundationOne Dx genomic profiling may take place as follows:

* Tumour Specimen: Acceptable samples include formalin-fixed, paraffin embedded (FFPE) tissue (preferred) or FFPE specimens, including core needle biopsies, fine-needle aspirates and effusion cytologies.
* Tumour Testing (optional): archival tumour specimens, where available, will be tested for mutations in HRR genes including BRCA1 and BRCA2 and other genomic alterations using the FoundationOne Dx genomic profile.

Intervention Type GENETIC

Follow-up

Patients who test positive for a gBRCA gene mutation, and/or sBRCA or other HRR gene mutations (optional testing), will be followed prospectively for assessment of treatment patterns and associated clinical outcomes up to 30-months.

\- Patients who test negative for gBRCA gene mutations, sBRCA and other HRR gene mutations, no further data will be collected post baseline. Patients presenting other genomic alterations that are identified by the FoundationOne Dx genomic profile will not continue beyond baseline as part of this study.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Provision of signed, written and dated informed consent.
2. Adult females (according to the age of majority/adulthood as defined by local regulations).
3. Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease.
4. Initiated treatment with 1st line systemic cytotoxic chemotherapy (not hormonal therapy) for metastatic breast cancer in the last 90 days and, at that time, are considered to have exhausted hormone therapy options (if HR+ve).

Exclusion Criteria

1. Previous enrolment in this study.
2. Involvement in the planning and/or conduct of this study (applies to both AstraZeneca staff and/or staff at the study site).
3. Current participation in a clinical study with an investigational oncology product.
4. Previous PARPi therapy, including, but not limited to, participation in a previous clinical study that included PARPi therapy.
5. Current commencement of PARPi treatment.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Quintiles; University of Tubingen - Germany

UNKNOWN

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Research Site

Santa Barbara, California, United States

Site Status

Research Site

Denver, Colorado, United States

Site Status

Research Site

Hialeah, Florida, United States

Site Status

Research Site

Dallas, Texas, United States

Site Status

Research Site

Denton, Texas, United States

Site Status

Research Site

Flower Mound, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Houston, Texas, United States

Site Status

Research Site

Paris, Texas, United States

Site Status

Research Site

San Antonio, Texas, United States

Site Status

Research Site

The Woodlands, Texas, United States

Site Status

Research Site

Newport News, Virginia, United States

Site Status

Research Site

Vancouver, Washington, United States

Site Status

Research Site

Wenatchee, Washington, United States

Site Status

Research Site

Redcliffe, Queensland, Australia

Site Status

Research Site

Kurralta Park, South Australia, Australia

Site Status

Research Site

Ballarat, Victoria, Australia

Site Status

Research Site

Dobrich, , Bulgaria

Site Status

Research Site

Rousse, , Bulgaria

Site Status

Research Site

Sofia, , Bulgaria

Site Status

Research Site

Kingston, Ontario, Canada

Site Status

Research Site

Kitchener, Ontario, Canada

Site Status

Research Site

Chicoutimi, Quebec, Canada

Site Status

Research Site

Québec, , Canada

Site Status

Research Site

Tübingen, , Germany

Site Status

Research Site

Budapest, , Hungary

Site Status

Research Site

Szeged, , Hungary

Site Status

Research Site

Szekszárd, , Hungary

Site Status

Research Site

Szolnok, , Hungary

Site Status

Research Site

Carpi, Modena, Italy

Site Status

Research Site

Castellanza, Varese, Italy

Site Status

Research Site

Milan, , Italy

Site Status

Research Site

Pavia, , Italy

Site Status

Research Site

Reggio Emilia, , Italy

Site Status

Research Site

Kamogawa-shi, Chiba, Japan

Site Status

Research Site

Matsuyama, Ehime, Japan

Site Status

Research Site

Fukuoka, Fukuoka, Japan

Site Status

Research Site

Sapporo, Hokkaido, Japan

Site Status

Research Site

Sendai, Miyagi, Japan

Site Status

Research Site

Osaka, Osaka, Japan

Site Status

Research Site

Chūōku, Tokyo-To, Japan

Site Status

Research Site

Brzozów, , Poland

Site Status

Research Site

Opole, , Poland

Site Status

Research Site

Warsaw, , Poland

Site Status

Research Site

Wałbrzych, , Poland

Site Status

Research Site

Wieliszew, , Poland

Site Status

Research Site

Wroclaw, , Poland

Site Status

Research Site

Żory, , Poland

Site Status

Research Site

Chelyabinsk, , Russia

Site Status

Research Site

Krasnodar, , Russia

Site Status

Research Site

Novosibirsk, , Russia

Site Status

Research Site

Omsk, , Russia

Site Status

Research Site

Pyatigorsk, , Russia

Site Status

Research Site

Ryazan, , Russia

Site Status

Research Site

Tomsk, , Russia

Site Status

Research Site

Goyang-si, Gyeonggi-do, South Korea

Site Status

Research Site

Seongnam-si, Gyeonggi-do, South Korea

Site Status

Research Site

Busan, , South Korea

Site Status

Research Site

Seoul, , South Korea

Site Status

Research Site

Ulsan, , South Korea

Site Status

Research Site

Terrassa, Barcelona, Spain

Site Status

Research Site

A Coruña, La Coruña, Spain

Site Status

Research Site

Alcorcón, Madrid, Spain

Site Status

Research Site

San Sebastián de los Reyes, Madrid, Spain

Site Status

Research Site

Barcelona, , Spain

Site Status

Research Site

Burgos, , Spain

Site Status

Research Site

Girona, , Spain

Site Status

Research Site

Huelva, , Spain

Site Status

Research Site

Changhua, , Taiwan

Site Status

Research Site

Kaohsiung City, , Taiwan

Site Status

Research Site

Taichung, , Taiwan

Site Status

Research Site

Tainan City, , Taiwan

Site Status

Research Site

Taipei, , Taiwan

Site Status

Research Site

Adana, , Turkey (Türkiye)

Site Status

Research Site

Ankara, , Turkey (Türkiye)

Site Status

Research Site

Antalya, , Turkey (Türkiye)

Site Status

Research Site

Diyarbakır, , Turkey (Türkiye)

Site Status

Research Site

Istanbul, , Turkey (Türkiye)

Site Status

Research Site

Izmir, , Turkey (Türkiye)

Site Status

Research Site

Kocaeli, , Turkey (Türkiye)

Site Status

Research Site

Sakarya, , Turkey (Türkiye)

Site Status

Research Site

Samsun, , Turkey (Türkiye)

Site Status

Research Site

Tekirdağ, , Turkey (Türkiye)

Site Status

Research Site

Trabzon, , Turkey (Türkiye)

Site Status

Research Site

Van, , Turkey (Türkiye)

Site Status

Research Site

Huntingdon, Cambridgeshire, United Kingdom

Site Status

Research Site

Peterborough, Cambridgeshire, United Kingdom

Site Status

Research Site

Truro, Cornwall, United Kingdom

Site Status

Research Site

Derby, Derbyshire, United Kingdom

Site Status

Research Site

Exeter, Devon, United Kingdom

Site Status

Research Site

Worthing, East Sussex, United Kingdom

Site Status

Research Site

London, Greater London, United Kingdom

Site Status

Research Site

Blackpool, Lancashire, United Kingdom

Site Status

Research Site

Lancaster, Lancashire, United Kingdom

Site Status

Research Site

Stoke-on-Trent, Staffordshire, United Kingdom

Site Status

Research Site

Warwick, Warwickshire, United Kingdom

Site Status

Research Site

Wolverhampton, West Midlands, United Kingdom

Site Status

Research Site

Huddersfield, West Yorkshire, United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Bulgaria Canada Germany Hungary Italy Japan Poland Russia South Korea Spain Taiwan Turkey (Türkiye) United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Koh SJ, Ohsumi S, Takahashi M, Fukuma E, Jung KH, Ishida T, Dai MS, Chang CH, Dalvi T, Walker G, Bennett J, O'Shaughnessy J, Balmana J. Prevalence of mutations in BRCA and homologous recombination repair genes and real-world standard of care of Asian patients with HER2-negative metastatic breast cancer starting first-line systemic cytotoxic chemotherapy: subgroup analysis of the global BREAKOUT study. Breast Cancer. 2022 Jan;29(1):92-102. doi: 10.1007/s12282-021-01283-4. Epub 2021 Aug 31.

Reference Type DERIVED
PMID: 34467476 (View on PubMed)

O'Shaughnessy J, Brezden-Masley C, Cazzaniga M, Dalvi T, Walker G, Bennett J, Ohsumi S. Prevalence of germline BRCA mutations in HER2-negative metastatic breast cancer: global results from the real-world, observational BREAKOUT study. Breast Cancer Res. 2020 Oct 27;22(1):114. doi: 10.1186/s13058-020-01349-9.

Reference Type DERIVED
PMID: 33109210 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

D0816R00012

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

BRCA Founder OutReach (BFOR) Study
NCT03351803 ACTIVE_NOT_RECRUITING