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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT03078036

Collaborator

Quintiles; University of Tubingen - Germany (Other)

873

Enrollment

Locations

26.2

Actual Duration (Months)

8.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Genetic: Germline BRCA Test (blood) Genetic: FoundationOne Dx Genomic Profile (archival Tumour Specimen) Other: Follow-up

Detailed 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.

Study Design

Study Type:

Observational

Actual Enrollment :

873 participants

Observational Model:

Cohort

Time Perspective:

Other

Official Title:

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

Actual Study Start Date :

Mar 13, 2017

Actual Primary Completion Date :

May 20, 2019

Actual Study Completion Date :

May 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.	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.) 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. 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.

Arm

Intervention/Treatment

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.

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.)

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.

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.

Outcome Measures

Primary Outcome Measures

BRCA Mutational status (BRCA1 mutated and/or BRCA2 mutated or BRCA wild type). [At one time point at inclusion in the study up to 12 months after the beginning of the study.]
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).

Secondary Outcome Measures

Descriptive statistics for treatments administered by line of therapy from 1st line metastatic breast cancer. [2.5 years (30 months) since the beginning of the study.]
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.
Progression free survival by line of therapy [2.5 years (30 months) since the beginning of the study.]
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.
Overall survival by line of therapy [2.5 years (30 months) since the beginning of the study.]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed, written and dated informed consent.
Adult females (according to the age of majority/adulthood as defined by local regulations).
Histologically or cytologically confirmed HER2-ve breast cancer with evidence of metastatic disease.
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:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Santa Barbara	California	United States	93105
2	Research Site	Denver	Colorado	United States	80218
3	Research Site	Hialeah	Florida	United States	33012
4	Research Site	Dallas	Texas	United States	75246
5	Research Site	Denton	Texas	United States	76210
6	Research Site	Flower Mound	Texas	United States	75028
7	Research Site	Houston	Texas	United States	77024
8	Research Site	Houston	Texas	United States	77089
9	Research Site	Paris	Texas	United States	75460
10	Research Site	San Antonio	Texas	United States	78217
11	Research Site	The Woodlands	Texas	United States	77380
12	Research Site	Newport News	Virginia	United States	23601
13	Research Site	Vancouver	Washington	United States	98684
14	Research Site	Wenatchee	Washington	United States	98801
15	Research Site	Redcliffe	Queensland	Australia
16	Research Site	Kurralta Park	South Australia	Australia
17	Research Site	Ballarat	Victoria	Australia
18	Research Site	Dobrich		Bulgaria
19	Research Site	Ruse		Bulgaria
20	Research Site	Sofia		Bulgaria
21	Research Site	Kingston	Ontario	Canada	K7L 5P9
22	Research Site	Kitchener	Ontario	Canada	N2G 1G3
23	Research Site	Chicoutimi	Quebec	Canada	G7H 5H6
24	Research Site	Quebec		Canada	G1S 4L8
25	Research Site	Tubingen		Germany
26	Research Site	Budapest		Hungary
27	Research Site	Szeged		Hungary
28	Research Site	Szekszard		Hungary
29	Research Site	Szolnok		Hungary
30	Research Site	Carpi	Modena	Italy
31	Research Site	Castellanza	Varese	Italy
32	Research Site	Milano		Italy
33	Research Site	Pavia		Italy
34	Research Site	Reggio Emilia		Italy
35	Research Site	Kamogawa-shi	Chiba-Ken	Japan
36	Research Site	Matsuyama-shi	Ehime-Ken	Japan
37	Research Site	Fukuoka-shi	Fukuoka-Ken	Japan
38	Research Site	Sapporo-shi	Hokkaido	Japan
39	Research Site	Sendai-shi	Miyagi-Ken	Japan
40	Research Site	Osaka-shi	Osaka-Fu	Japan
41	Research Site	Chuo-ku	Tokyo-To	Japan
42	Research Site	Goyang-si	Gyeonggi-do	Korea, Republic of
43	Research Site	Seongnam-si,	Gyeonggi-do	Korea, Republic of
44	Research Site	Seongnam-si	Gyeonggi-do	Korea, Republic of
45	Research Site	Busan		Korea, Republic of
46	Research Site	Seoul		Korea, Republic of
47	Research Site	Ulsan		Korea, Republic of
48	Research Site	Brzozow		Poland
49	Research Site	Opole		Poland
50	Research Site	Walbrzych		Poland
51	Research Site	Warszawa		Poland
52	Research Site	Wieliszew		Poland
53	Research Site	Wroclaw		Poland
54	Research Site	Zory		Poland
55	Research Site	Chelyabinsk		Russian Federation
56	Research Site	Krasnodar		Russian Federation
57	Research Site	Novosibirsk		Russian Federation
58	Research Site	Omsk		Russian Federation
59	Research Site	Pyatigorsk		Russian Federation
60	Research Site	Ryazan		Russian Federation
61	Research Site	Tomsk		Russian Federation
62	Research Site	Terrassa	Barcelona	Spain
63	Research Site	A Coruna	La Coruña	Spain
64	Research Site	Alcorcon	Madrid	Spain
65	Research Site	San Sebastian de los Reyes	Madrid	Spain
66	Research Site	Barcelona		Spain
67	Research Site	Burgos		Spain
68	Research Site	Girona		Spain
69	Research Site	Huelva		Spain
70	Research Site	Changhua		Taiwan
71	Research Site	Kaohsiung		Taiwan
72	Research Site	Taichung		Taiwan
73	Research Site	Tainan		Taiwan
74	Research Site	Taipei		Taiwan
75	Research Site	Adana		Turkey
76	Research Site	Ankara		Turkey
77	Research Site	Antalya		Turkey
78	Research Site	Diyarbakir		Turkey
79	Research Site	Istanbul		Turkey
80	Research Site	Izmir		Turkey
81	Research Site	Kocaeli		Turkey
82	Research Site	Sakarya		Turkey
83	Research Site	Samsun		Turkey
84	Research Site	Tekirdag		Turkey
85	Research Site	Trabzon		Turkey
86	Research Site	Van		Turkey
87	Research Site	Huntingdon	Cambridgeshire	United Kingdom
88	Research Site	Peterborough	Cambridgeshire	United Kingdom
89	Research Site	Truro	Cornwall	United Kingdom
90	Research Site	Derby	Derbyshire	United Kingdom
91	Research Site	Exeter	Devon	United Kingdom
92	Research Site	Worthing	East Sussex	United Kingdom
93	Research Site	London	Greater London	United Kingdom
94	Research Site	Blackpool	Lancashire	United Kingdom
95	Research Site	Lancaster	Lancashire	United Kingdom
96	Research Site	Stoke on Trent	Staffordshire	United Kingdom
97	Research Site	Warwick	Warwickshire	United Kingdom
98	Research Site	Wolverhampton	West Midlands	United Kingdom
99	Research Site	Huddersfield	West Yorkshire	United Kingdom

Sponsors and Collaborators

AstraZeneca
Quintiles; University of Tubingen - Germany

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Related Info

Publications

None provided.

Responsible Party:

AstraZeneca

ClinicalTrials.gov Identifier:

NCT03078036

Other Study ID Numbers:

D0816R00012

First Posted:

Mar 13, 2017

Last Update Posted:

May 20, 2020

Last Verified:

May 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by AstraZeneca

HER2-ve metastatic breast cancer

gBRCA, sBRCA and HRR gene mutations

Additional relevant MeSH terms:

Breast Neoplasms

Study Results

No Results Posted as of May 20, 2020