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

Breast Cancer Clinical Trial

— BREAKOUT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03078036
• Other study ID #: D0816R00012
• Status: Completed
• Start date: March 13, 2017
• Est. completion date: May 20, 2019

Study information

• Verified date: May 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 873
• Est. completion date: May 20, 2019
• Est. primary completion date: May 20, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Genetic:
• 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.)
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Australia	Research Site	Ballarat	Victoria
Australia	Research Site	Kurralta Park	South Australia
Australia	Research Site	Redcliffe	Queensland
Bulgaria	Research Site	Dobrich
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sofia
Canada	Research Site	Chicoutimi	Quebec
Canada	Research Site	Kingston	Ontario
Canada	Research Site	Kitchener	Ontario
Canada	Research Site	Quebec
Germany	Research Site	Tubingen
Hungary	Research Site	Budapest
Hungary	Research Site	Szeged
Hungary	Research Site	Szekszard
Hungary	Research Site	Szolnok
Italy	Research Site	Carpi	Modena
Italy	Research Site	Castellanza	Varese
Italy	Research Site	Milano
Italy	Research Site	Pavia
Italy	Research Site	Reggio Emilia
Japan	Research Site	Chuo-ku	Tokyo-To
Japan	Research Site	Fukuoka-shi	Fukuoka-Ken
Japan	Research Site	Kamogawa-shi	Chiba-Ken
Japan	Research Site	Matsuyama-shi	Ehime-Ken
Japan	Research Site	Osaka-shi	Osaka-Fu
Japan	Research Site	Sapporo-shi	Hokkaido
Japan	Research Site	Sendai-shi	Miyagi-Ken
Korea, Republic of	Research Site	Busan
Korea, Republic of	Research Site	Goyang-si	Gyeonggi-do
Korea, Republic of	Research Site	Seongnam-si	Gyeonggi-do
Korea, Republic of	Research Site	Seongnam-si,	Gyeonggi-do
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Ulsan
Poland	Research Site	Brzozow
Poland	Research Site	Opole
Poland	Research Site	Walbrzych
Poland	Research Site	Warszawa
Poland	Research Site	Wieliszew
Poland	Research Site	Wroclaw
Poland	Research Site	Zory
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Krasnodar
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Omsk
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Tomsk
Spain	Research Site	A Coruna	La Coruña
Spain	Research Site	Alcorcon	Madrid
Spain	Research Site	Barcelona
Spain	Research Site	Burgos
Spain	Research Site	Girona
Spain	Research Site	Huelva
Spain	Research Site	San Sebastian de los Reyes	Madrid
Spain	Research Site	Terrassa	Barcelona
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Turkey	Research Site	Adana
Turkey	Research Site	Ankara
Turkey	Research Site	Antalya
Turkey	Research Site	Diyarbakir
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Kocaeli
Turkey	Research Site	Sakarya
Turkey	Research Site	Samsun
Turkey	Research Site	Tekirdag
Turkey	Research Site	Trabzon
Turkey	Research Site	Van
United Kingdom	Research Site	Blackpool	Lancashire
United Kingdom	Research Site	Derby	Derbyshire
United Kingdom	Research Site	Exeter	Devon
United Kingdom	Research Site	Huddersfield	West Yorkshire
United Kingdom	Research Site	Huntingdon	Cambridgeshire
United Kingdom	Research Site	Lancaster	Lancashire
United Kingdom	Research Site	London	Greater London
United Kingdom	Research Site	Peterborough	Cambridgeshire
United Kingdom	Research Site	Stoke on Trent	Staffordshire
United Kingdom	Research Site	Truro	Cornwall
United Kingdom	Research Site	Warwick	Warwickshire
United Kingdom	Research Site	Wolverhampton	West Midlands
United Kingdom	Research Site	Worthing	East Sussex
United States	Research Site	Dallas	Texas
United States	Research Site	Denton	Texas
United States	Research Site	Denver	Colorado
United States	Research Site	Flower Mound	Texas
United States	Research Site	Hialeah	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Newport News	Virginia
United States	Research Site	Paris	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	Santa Barbara	California
United States	Research Site	The Woodlands	Texas
United States	Research Site	Vancouver	Washington
United States	Research Site	Wenatchee	Washington

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Quintiles; University of Tubingen - Germany

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	BRCA Mutational status (BRCA1 mutated and/or BRCA2 mutated or BRCA wild type).	The prevalence of gBRCA gene mutations will be evaluated by calculating the proportion of patients that test positive for a gBRCA gene mutation (BRCA1 mutated and/or BRCA2 mutated).	At one time point at inclusion in the study up to 12 months after the beginning of the study.
Secondary	Descriptive statistics for treatments administered by line of therapy from 1st line metastatic breast cancer.	Treatment patterns will be described by line of therapy. Treatment combinations, number of cycles per line, schedules, durations, and reason for discontinuation will be summarized descriptively.	2.5 years (30 months) since the beginning of the study.
Secondary	Progression free survival by line of therapy	Progression free survival (in months) for each line of treatment, defined as the time from the date of start of each line of treatment to the documented date of progression as determined by the investigator (radiologic or symptomatic), or death from any cause in the absence of progression.	2.5 years (30 months) since the beginning of the study.
Secondary	Overall survival by line of therapy	Overall survival (OS) defined as the time from the start date of first line chemotherapy in the metastatic setting until the date of death due to any cause, assessed up to 30 months. In addition, OS since diagnosis of metastatic breast cancer and OS since the start of each subsequent therapy will be estimated.	2.5 years (30 months) since the beginning of the study.

External Links

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