Clinical trial NCT01479101: NBRST: Prospective Neo-adjuvant REGISTRY Trial
Official title: Prospective Neo-adjuvant REGISTRY Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry - Symphony Trial (NBRST) (Pronounced "in Breast")
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Keywords: neo adjuvant, breast cancer
Lead sponsor: Agendia
Sponsor class: INDUSTRY
First posted: 2011-11-24
Enrollment: 1142
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy.

Brief summary: The scope of this registry study is to measure chemosensitivity as defined by pCR (primary endpoint), or endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1), a primary endpoint for neo-adjuvant endocrine therapy and a secondary endpoint for neoadjuvant chemotherapy), metastasis-free survival and relapse-free survival(secondary endpoints) in molecular subgroups, determined by the established MammaPrint, BluePrint, Targetprint and Theraprint profiles in addition to possible novel expression profiles.

Detailed description: This will be a prospective observational, case-only study linking MammaPrint, BluePrint, TargetPrint, TheraPrint and possible additional profiles of interest to treatment response and Distant Metastases Free Survival (DMFS) and Relapse Free Survival (RFS). Only patients who receive neo-adjuvant therapy can participate.

For this project, approximately 50-70 institutions in the US will be invited to contribute clinical patient data from enrolled patients after a MammaPrint, TargetPrint, BluePrint and TheraPrint test has been successfully performed and the patient has started neo-adjuvant therapy.

Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative.

The clinical data is to be entered online at 4 time points; amounting to four Case Report Forms (CRFs). Data will be collected on an ongoing basis, the first CRF must be completed within 6 weeks after the MammaPrint, BluePrint, TargetPrint, and TheraPrint result was provided. The second CRF should be completed 4 weeks after definitive surgery. CRF 3 and CRF4 will be completed 2-3 and 5 years after surgery.

It is expected that we will enroll around 1000 patients in 4 years.

OBJECTIVES

* Measure chemosensitivity (as defined by pCR) or endocrine sensitivity (as defined by decrease in longest tumor diameter or RCB1)in the molecular subgroups as determined by combining MammaPrint and BluePrint results.
* Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.
* Compare local IHC and FISH results (if available) with TargetPrint results. Compare the three BluePrint molecular subgroups with IHC-based subtype classification.
* Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.
* Assess the 2-3 and 5 years DMFS and RFS for the different molecular subgroups.
* Measure chemosensitivity or endocrine sensitivity correlation with novel expression profiles.

Eligibility criteria: Inclusion Criteria:

* Women with histologically proven breast cancer, who have started or are scheduled to start neo-adjuvant chemotherapy therapy or neo-adjuvant hormone therapy, after successful MammaPrint assay
* Age 18-90
* Written informed consent

Exclusion Criteria:

* Patients who have had excisional biopsy or axillary dissection Patients with confirmed distant metastatic disease
* Tumor sample shipped to Agendia with ≤ 30% tumor cells or that fails QA or QC criteria
* Patients who have had any prior chemotherapy, radiotherapy, or endocrine therapy for the treatment of breast cancer
* Any serious uncontrolled intercurrent infections, or other serious uncontrolled concomitant disease

Primary outcomes:
measure: Chemosensitivity as defined by pCR
timeFrame: Up to 6 months
measure: Endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1)
timeFrame: Up to 6 months
Secondary outcomes:
measure: Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.
timeFrame: Up to 6 months.
measure: Assess metastasis-free survival and relapse-free survival in molecular subgroups, determined by the established MammaPrint, BluePrint, profiles.
timeFrame: At -2-3 years and 5 years after definitive surgery.
measure: Compare local IHC and FISH results (if available) with TargetPrint results.
timeFrame: Baseline; before start of neo-adjuvant therapy.
measure: Compare the three BluePrint molecular subgroups with IHC-based subtype classification.
timeFrame: Baseline; before start of neo-adjuvant therapy.
measure: Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.
timeFrame: Baseline; before start neo-adjuvant therapy.
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Arizona Center for Cancer Care
state: Arizona
city: Scottsdale
country: United States
facility: 21 Century Oncology
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Summit Comprehensive Cancer Center
state: California
city: Fresno
country: United States
facility: Fresno Breast Surgery
state: California
city: Long Beach
country: United States
facility: BreastLink
state: California
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Monterey
country: United States
facility: Community Hospital of Monterey Peninsula
state: California
city: Oakland
country: United States
facility: Alta Bates
state: California
city: Palm Springs
country: United States
facility: Comprehensive Cancer Center - Palm Springs
state: California
city: Roseville
country: United States
facility: Sutter Roseville Medical Center
state: California
city: San Diego
country: United States
facility: SHARP Memorial
state: California
city: Santa Rosa
country: United States
facility: Redwood Regional
state: California
city: West Hills
country: United States
facility: Wellness Oncology Hematology
state: California
city: West Hills
country: United States
facility: Wellness Oncology Hematology
state: California
city: Denver
country: United States
facility: Exempla Health St Joseph
state: Colorado
city: Greenwich
country: United States
facility: Greenwich Hospital
state: Connecticut
city: Stamford
country: United States
facility: Stamford Hospital
state: Connecticut
city: Daytona Beach
country: United States
facility: Halifax Health Center for Oncology
state: Florida
city: Daytona Beach
country: United States
facility: Florida Hospital Memorial Medical Center
state: Florida
city: Fort Myers
country: United States
facility: 21st Century Oncology
state: Florida
city: Jacksonville
country: United States
facility: St. Vincent Healthcare
state: Florida
city: Lake Worth
country: United States
facility: The Breast Institute at JFK Medical Center
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research
state: Florida
city: Miami
country: United States
facility: Baptist Health South Florida
state: Florida
city: Decatur
country: United States
facility: Dekalb Medical
state: Georgia
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Savannah
country: United States
facility: Center for Breast Care
state: Georgia
city: Bloomingdale
country: United States
facility: Advanced Breast Care Specialists
state: Illinois
city: Elk Grove Village
country: United States
facility: University Surgical Consultants
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Skokie
country: United States
facility: Hematology/Oncology of The North Shore
state: Illinois
city: Evansville
country: United States
facility: Evansville Surgical Associates
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research
state: Indiana
city: Shreveport
country: United States
facility: Willis-Knighton Cancer Center
state: Louisiana
city: Lanham
country: United States
facility: Signature Breast Care
state: Maryland
city: Burton
country: United States
facility: McLaren Health Care
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Great Lakes Cancer Management Specialists
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute
state: Michigan
city: Kansas City
country: United States
facility: St Lukes Cancer Center
state: Missouri
city: Saint Louis
country: United States
facility: Christian Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: Compehensive Cancer Care of Nevada
state: Nevada
city: Willingboro
country: United States
facility: Virtua Health
state: New Jersey
city: Cortlandt Manor
country: United States
facility: Ashikari Breast Center
state: New York
city: East Syracuse
country: United States
facility: Hematology Oncology Associates of Central New York
state: New York
city: Flushing
country: United States
facility: Theresa & Eugene M. Lang Research Center
state: New York
city: Akron
country: United States
facility: Akron General Hospital
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Allentown
country: United States
facility: Breast Care Specialists
state: Pennsylvania
city: Kittanning
country: United States
facility: ACMH Cancer Center
state: Pennsylvania
city: Langhorne
country: United States
facility: St. Mary Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: St. Clair Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: The Breast Place
state: South Carolina
city: Charleston
country: United States
facility: Cancer Specialists of Charleston
state: South Carolina
city: Murrells Inlet
country: United States
facility: Coastal Carolina Breast Center
state: South Carolina
city: Nashville
country: United States
facility: Nashville Breast Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University
state: Texas
city: Austin
country: United States
facility: Austin Cancer Center
state: Texas
city: Dallas
country: United States
facility: Dallas Surgical Group
state: Texas
city: Dallas
country: United States
facility: Texas Health
state: Texas
city: Edinburg
country: United States
facility: McAllen Oncology
state: Texas
city: Houston
country: United States
facility: East Houston General Surgery
state: Texas
city: San Antonio
country: United States
facility: Kathryn A. Wagner Private Practice
state: Texas
city: San Antonio
country: United States
facility: Radiation Oncology of San Antonio
state: Texas
city: Charlottesville
country: United States
facility: Virginia Breast Care
state: Virginia
city: Harrisonburg
country: United States
facility: Rockingham Memorial Hospital
state: Virginia
city: Lynchburg
country: United States
facility: Lynchburg Hematology Oncology Clinic
state: Virginia
city: Midlothian
country: United States
facility: Bon Secours Virginia Breast Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Spokane
country: United States
facility: Rockwood Clinic
state: Washington
city: Green Bay
country: United States
facility: Bellin Hospital
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia St. Marys Cancer Center
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital
state: Wisconsin
city: Wauwatosa
country: United States
facility: Wheaton Franciscan Healthcare
state: Wisconsin
Study officials:
affiliation: Nashville Breast Center
name: Pat Whitworth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Reinsch Pierce Family Center for Breast Health
name: Stephanie Akbari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Breast Care Specialists
name: Mark Gittleman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dallas Surgical Group
name: Peter Beitsch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Whitworth PW, Beitsch PD, Murray MK, Richards PD, Mislowsky A, Dul CL, Pellicane JV, Baron PL, Rahman RL, Lee LA, Dupree BB, Kelemen PR, Ashikari AY, Budway RJ, Lopez-Penalver C, Dooley W, Wang S, Dauer P, Menicucci AR, Yoder EB, Finn C, Blumencranz LE, Audeh W. Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy. JCO Precis Oncol. 2022 Sep;6:e2200197. doi: 10.1200/PO.22.00197.
citation: Whitworth PW, Beitsch PD, Pellicane JV, Baron PL, Lee LA, Dul CL, Murray MK, Gittleman MA, Budway RJ, Rahman RL, Kelemen PR, Dooley WC, Rock DT, Cowan KH, Lesnikoski BA, Barone JL, Ashikari AY, Dupree BB, Wang S, Menicucci AR, Yoder EB, Finn C, Corcoran K, Blumencranz LE, Audeh W; NBRST Investigators Group. Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature. JCO Precis Oncol. 2022 Apr;6(1):e2100463. doi: 10.1200/PO.21.00463.