Clinical trial NCT04875351: Breast Cancer Index (BCI) Registry
Official title: Breast Cancer Index (BCI) Registry
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Keywords: Breast Neoplasm
Invasive Breast Carcinoma
Early Stage (I, II or III) Breast Cancer
Hormone Receptor positive (HR+) Breast Cancer
Extended Endocrine Therapy
Lead sponsor: Biotheranostics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 3465
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will include patients with stage I-III HR+ breast cancer that have signed an informed consent. Patients seen within a physician practice participating in the registry are potential candidates after meeting eligibility criteria requirements.

Brief summary: The purpose of the Breast Cancer Index (BCI) Registry study is to conduct a large scale, population-based prospective registry to evaluate long-term clinical outcome, clinical impact, medication adherence and quality of life in hormone receptor positive (HR+) early-stage breast cancer patients receiving BCI testing as part of routine clinical care to inform extended endocrine therapy.

Detailed description: The BCI Registry is designed as a large-scale data registry and biospecimen repository to evaluate the clinical outcome of hormone receptor positive (HR+) early-stage breast cancer patients completing primary adjuvant endocrine therapy and are considering extended endocrine treatment. The impact of BCI test results on extended endocrine therapy decision-making and clinical use patterns will be characterized. Extended endocrine therapy-specific medication adherence will be assessed annually. Primary tumor tissue will be collected for scientific research purposes including molecular profiling and for correlative studies. The sample size will consist of approximately 3,000 subjects across 30-50 sites in the United States.

The BCI registry will recruit patients with HR+ stage I to III breast cancer following an initial 4-7 years of adjuvant endocrine therapy that will have BCI testing performed as part of routine clinical care and meet the inclusion/exclusion criteria. After signing the informed consent form (ICF) during screening, physicians and patients will complete the pre-test Decision Impact Questionnaire. Upon ordering BCI by the treating physician, primary tumor tissue obtained from the patient during previous breast-conserving surgery or mastectomy will be requested by Biotheranostics to perform BCI testing at Biotheranostics' CLIA certified and CAP accredited clinical laboratory in San Diego, CA. Following BCI testing, the physician will share and discuss the BCI results with their patients and recommend to either stop or extend endocrine therapy for an additional 5 years. The impact of the BCI test results on extended endocrine therapy decision-making will be assessed using the post-test Decision Impact Questionnaire, which will be completed by both physicians and patients. In addition, medication adherence will be evaluated in patients that are recommended for or elect to continue treatment to complete 10 years of adjuvant endocrine therapy.

BCI reports both a prognostic and predictive result and has been shown to significantly stratify patients based on the risk of late distant recurrence as well as to predict the likelihood of benefit from endocrine therapy in multiple prospective-retrospective studies within randomized controlled trial cohorts. The BCI registry study will determine the long-term outcome and BCI test performance to add prospective validation for the prognostic and predictive capabilities of BCI. In this context, the impact of BCI test results on treatment decision-making and subsequently prescribed treatments will be characterized.

Analysis of BCI test performance with long-term outcome will be performed by Kaplan-Meier analysis with log-rank test to assess the statistical significance of the risk stratification by BCI risk groups. Cox proportional hazards regression will be used to derive the hazard ratios (HR) and the associated 95% confidence intervals for the comparison of BCI risk groups. Univariate and multivariate analysis adjusting for clinical factors such as age, tumor size, grade, and treatment background (adjuvant endocrine therapy and chemotherapy) will be conducted. Descriptive statistics will be used to evaluate the decision-impact and medication adherence scores of patients enrolled in the study.

Each participating site will maintain appropriate medical and research records for this trial, in compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional requirements for the protection of confidentiality of subjects. As part of participating in a Biotheranostics-sponsored study, each site will permit authorized representatives of the sponsor and regulatory agencies to examine clinical records for the purposes of quality assurance reviews, audits and evaluation of the study progress. The clinical trial manager will be in regular contact with the site research leader to check on progress and address any queries that they may have. Sites may be suspended from participating in the registry in the event of serious and persistent non-compliance with the protocol and/or Good Clinical Practice. Any major problems identified will be reported to the Trial Management Team and if necessary, the relevant regulatory bodies.

Eligibility criteria: Inclusion Criteria:

* Early stage (I, II or III) female breast cancer patients, who have completed 4-7 years of primary adjuvant endocrine therapy
* Patient was diagnosed with invasive breast carcinoma (ductal, lobular, or mixed ductal/lobular).
* The primary tumor was hormone receptor positive (HR+), i.e. estrogen receptor-positive and/or progesterone receptor-positive.
* The primary tumor was HER2 negative or positive and node-negative or node-positive with 1-3 positive lymph nodes.
* Subject has pre-treatment breast tumor tissue \[formalin fixed and paraffin embedded (FFPE)\] from a previous breast-conserving surgery, mastectomy or core needle biopsy available for testing by the Sponsor.

Exclusion Criteria:

* Patient has distant metastatic disease (M1).
* Patient was diagnosed with metaplastic breast cancer, carcinosarcoma, sarcoma, neuroendocrine carcinoma, adenoid cystic carcinoma, or phyllodes tumor.

Primary outcomes:
measure: To determine BCI test performance by evaluating the long-term outcome of BCI risk groups over the follow-up period.
timeFrame: 5 Years
measure: To determine medication adherence in patients undergoing extended endocrine therapy.
timeFrame: 5 Years
Secondary outcomes:
measure: To prospectively assess the impact of BCI on extended endocrine therapy decision-making.
timeFrame: 5 Years
measure: To correlate BCI results with molecular tumor profiles in early stage breast cancer.
timeFrame: 5 Years
Other outcomes:
Locations:
city: Daphne
country: United States
facility: Southern Cancer Center, P.C. - Daphne
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC - Mobile Infirmary
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC - Providence Hospital
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center, PC - Springhill Medical Center
state: Alabama
city: Glendale
country: United States
facility: Arizona Oncology Associates, PC - Glendale - Saguaro Cancer Center
state: Arizona
city: Goodyear
country: United States
facility: Arizona Oncology Associates, PC - Goodyear
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - Phoenix - Biltmore Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates, PC - Phoenix - Deer Valley
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Oncology Associates, PC - Scottsdale
state: Arizona
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - East Valley Cancer Center
state: Arizona
city: Santa Barbara
country: United States
facility: Sansum Clinic - Ridley-Tree Cancer Center
state: California
city: Solvang
country: United States
facility: Sansum Clinic - Ridley-Tree Cancer Center (Solvang)
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Center - Aurora
state: Colorado
city: Boulder
country: United States
facility: Rocky Mountain Cancer Center - Boulder
state: Colorado
city: Centennial
country: United States
facility: Rocky Mountain Cancer Center - Centennial
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Center - Colorado Springs
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center - Denver Midtown
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Cancer Center - Denver
state: Colorado
city: Englewood
country: United States
facility: Rocky Mountain Cancer Center - Swedish Medical Center
state: Colorado
city: Lakewood
country: United States
facility: Rocky Mountain Cancer Centers - Lakewood
state: Colorado
city: Littleton
country: United States
facility: Rocky Mountain Cancer Center - Littleton
state: Colorado
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Center - Lone Tree
state: Colorado
city: Longmont
country: United States
facility: Rocky Mountain Cancer Center - Longmont
state: Colorado
city: Pueblo
country: United States
facility: Rocky Mountain Cancer Center - Pueblo
state: Colorado
city: Thornton
country: United States
facility: Rocky Mountain Cancer Center - Thornton
state: Colorado
city: Palm Bay
country: United States
facility: Cancer Care Centers of Brevard, Inc.
state: Florida
city: Arlington Heights
country: United States
facility: Illinois Cancer Specialists - Arlington Heights
state: Illinois
city: Chicago Ridge
country: United States
facility: Affiliated Oncologists, LLC
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists - Niles
state: Illinois
city: Bethesda
country: United States
facility: Maryland Oncology Hematology, P.A. - Bethesda
state: Maryland
city: Brandywine
country: United States
facility: Maryland Oncology Hematology, P.A. - Brandywine
state: Maryland
city: Clinton
country: United States
facility: Maryland Oncology Hematology, P.A. - Clinton
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A. - Columbia
state: Maryland
city: Frederick
country: United States
facility: Maryland Oncology Hematology, P.A. - Frederick
state: Maryland
city: Lanham
country: United States
facility: Maryland Oncology Hematology, P.A. - Lanham
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. - Rockville - Aquilino Cancer Center
state: Maryland
city: Silver Spring
country: United States
facility: Maryland Oncology Hematology, P.A. - Silver Spring - White Oak Cancer Center
state: Maryland
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. - Albany Cancer Center
state: New York
city: Albany
country: United States
facility: New York Oncology Hematology, P.C. - Albany Medical Center
state: New York
city: Binghamton
country: United States
facility: Broome Oncology, LLC - Binghamton
state: New York
city: Clifton Park
country: United States
facility: New York Oncology Hematology, P.C. - Clifton Park Cancer Center
state: New York
city: Johnson City
country: United States
facility: Broome Oncology, LLC - Johnson City
state: New York
city: Bensalem
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Broomall
country: United States
facility: Consultants In Medical Oncology and Hematology, P.C.
state: Pennsylvania
city: Horsham
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Langhorne
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Sellersville
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Wynnewood
country: United States
facility: Alliance Cancer Specialists, PC
state: Pennsylvania
city: Abilene
country: United States
facility: Texas Oncology - Abilene
state: Texas
city: Allen
country: United States
facility: Texas Oncology - Allen
state: Texas
city: Amarillo
country: United States
facility: Texas Oncology - Amarillo
state: Texas
city: Arlington
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Arlington
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology - Beaumont
state: Texas
city: Beaumont
country: United States
facility: Texas Oncology - Beaumont Mamie McFaddin Ward Cancer Center
state: Texas
city: Bedford
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Carrollton
country: United States
facility: Texas Oncology - Carrollton
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Presbyterian Cancer Center Dallas
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Denison
country: United States
facility: Texas Oncology - Denison
state: Texas
city: Denton
country: United States
facility: Texas Oncology - Denton
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - El Paso Cancer Treatment Center Grandview
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - El Paso Cancer Treatment Center Gateway
state: Texas
city: El Paso
country: United States
facility: Texas Oncology - El Paso Cancer Treatment Center Joe Battle
state: Texas
city: Flower Mound
country: United States
facility: Texas Oncology - Flower Mound
state: Texas
city: Grapevine
country: United States
facility: Texas Oncology - DFWW
state: Texas
city: Harlingen
country: United States
facility: Texas Oncology - Harlingen
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Memorial City
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Willowbrook
state: Texas
city: Longview
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen
state: Texas
city: McKinney
country: United States
facility: Texas Oncology - McKinney
state: Texas
city: Midland
country: United States
facility: Texas Oncology - Midland
state: Texas
city: New Braunfels
country: United States
facility: Texas Oncology - New Braunfels
state: Texas
city: Odessa
country: United States
facility: Texas Oncology - Odessa
state: Texas
city: Palestine
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Paris
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano West
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Downtown
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Stone Oak
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology - Sugar Land
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology - The Woodlands
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Austin
state: Texas
city: Waco
country: United States
facility: Texas Oncology - Horizon Circle
state: Texas
city: Webster
country: United States
facility: Texas Oncology - Deke Slayton Cancer Center
state: Texas
city: Weslaco
country: United States
facility: Texas Oncology - Weslaco
state: Texas
city: Wichita Falls
country: United States
facility: Texas Oncology - Wichita Falls
state: Texas
city: Alexandria
country: United States
facility: Virginia Cancer Specialists, PC - Alexandria
state: Virginia
city: Arlington
country: United States
facility: Virginia Cancer Specialists, PC - Arlington
state: Virginia
city: Chesapeake
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC - Fairfax
state: Virginia
city: Gainesville
country: United States
facility: Virginia Cancer Specialists, PC - Gainesville
state: Virginia
city: Leesburg
country: United States
facility: Virginia Cancer Specialists, PC - Loudoun
state: Virginia
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Virginia Beach
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Williamsburg
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Winchester
country: United States
facility: Shenandoah Oncology, P.C.
state: Virginia
Study officials:
affiliation: US Oncology Network
name: Joyce A O'Shaughnessy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Biotheranostics, Inc.
name: Kai Treuner, PhD
role: STUDY_DIRECTOR
affiliation: Biotheranostics, Inc.
name: Amanda KL Anderson, PhD
role: STUDY_DIRECTOR
References:
citation: Noordhoek I, Treuner K, Putter H, Zhang Y, Wong J, Meershoek-Klein Kranenbarg E, Duijm-de Carpentier M, van de Velde CJH, Schnabel CA, Liefers GJ. Breast Cancer Index Predicts Extended Endocrine Benefit to Individualize Selection of Patients with HR+ Early-stage Breast Cancer for 10 Years of Endocrine Therapy. Clin Cancer Res. 2021 Jan 1;27(1):311-319. doi: 10.1158/1078-0432.CCR-20-2737. Epub 2020 Oct 27.
citation: Bartlett JMS, Sgroi DC, Treuner K, Zhang Y, Ahmed I, Piper T, Salunga R, Brachtel EF, Pirrie SJ, Schnabel CA, Rea DW. Breast Cancer Index and prediction of benefit from extended endocrine therapy in breast cancer patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial. Ann Oncol. 2019 Nov 1;30(11):1776-1783. doi: 10.1093/annonc/mdz289.
citation: Zhang Y, Schnabel CA, Schroeder BE, Jerevall PL, Jankowitz RC, Fornander T, Stal O, Brufsky AM, Sgroi D, Erlander MG. Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early- and late-distant recurrence. Clin Cancer Res. 2013 Aug 1;19(15):4196-205. doi: 10.1158/1078-0432.CCR-13-0804. Epub 2013 Jun 11.
citation: Sgroi DC, Sestak I, Cuzick J, Zhang Y, Schnabel CA, Schroeder B, Erlander MG, Dunbier A, Sidhu K, Lopez-Knowles E, Goss PE, Dowsett M. Prediction of late distant recurrence in patients with oestrogen-receptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol. 2013 Oct;14(11):1067-1076. doi: 10.1016/S1470-2045(13)70387-5. Epub 2013 Sep 12.
citation: Sgroi DC, Carney E, Zarrella E, Steffel L, Binns SN, Finkelstein DM, Szymonifka J, Bhan AK, Shepherd LE, Zhang Y, Schnabel CA, Erlander MG, Ingle JN, Porter P, Muss HB, Pritchard KI, Tu D, Rimm DL, Goss PE. Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker. J Natl Cancer Inst. 2013 Jul 17;105(14):1036-42. doi: 10.1093/jnci/djt146. Epub 2013 Jun 28.