NBRST: Prospective Neo-adjuvant REGISTRY Trial

Breast Cancer Clinical Trial

— NBRST  

Official title:

Prospective Neo-adjuvant REGISTRY Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry - Symphony Trial (NBRST) (Pronounced "in Breast")

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01479101
• Other study ID #: P0339 NBRST Registry
• Status: Completed
• Start date: July 2011
• Est. completion date: January 2021

Study information

• Verified date: January 2021
• Source: Agendia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1142
• Est. completion date: January 2021
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Other:
• MammaPrint 70-gene expression profile

• BluePrint 80 gene expression profile

Locations

Country	Name	City	State
United States	Akron General Hospital	Akron	Ohio
United States	Breast Care Specialists	Allentown	Pennsylvania
United States	Texas Tech University	Amarillo	Texas
United States	Austin Cancer Center	Austin	Texas
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Advanced Breast Care Specialists	Bloomingdale	Illinois
United States	McLaren Health Care	Burton	Michigan
United States	Cancer Specialists of Charleston	Charleston	South Carolina
United States	The Breast Place	Charleston	South Carolina
United States	Virginia Breast Care	Charlottesville	Virginia
United States	Ashikari Breast Center	Cortlandt Manor	New York
United States	Dallas Surgical Group	Dallas	Texas
United States	Texas Health	Dallas	Texas
United States	Florida Hospital Memorial Medical Center	Daytona Beach	Florida
United States	Halifax Health Center for Oncology	Daytona Beach	Florida
United States	Dekalb Medical	Decatur	Georgia
United States	Exempla Health St Joseph	Denver	Colorado
United States	Hematology Oncology Associates of Central New York	East Syracuse	New York
United States	McAllen Oncology	Edinburg	Texas
United States	University Surgical Consultants	Elk Grove Village	Illinois
United States	Evansville Surgical Associates	Evansville	Indiana
United States	Theresa & Eugene M. Lang Research Center	Flushing	New York
United States	21st Century Oncology	Fort Myers	Florida
United States	Fresno Breast Surgery	Fresno	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Arizona Center for Cancer Care	Glendale	Arizona
United States	Bellin Hospital	Green Bay	Wisconsin
United States	Greenwich Hospital	Greenwich	Connecticut
United States	Great Lakes Cancer Management Specialists	Grosse Pointe Woods	Michigan
United States	Rockingham Memorial Hospital	Harrisonburg	Virginia
United States	East Houston General Surgery	Houston	Texas
United States	St. Vincent Healthcare	Jacksonville	Florida
United States	St Lukes Cancer Center	Kansas City	Missouri
United States	ACMH Cancer Center	Kittanning	Pennsylvania
United States	The Breast Institute at JFK Medical Center	Lake Worth	Florida
United States	St. Mary Medical Center	Langhorne	Pennsylvania
United States	Signature Breast Care	Lanham	Maryland
United States	Compehensive Cancer Care of Nevada	Las Vegas	Nevada
United States	BreastLink	Long Beach	California
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Lynchburg Hematology Oncology Clinic	Lynchburg	Virginia
United States	Baptist Health South Florida	Miami	Florida
United States	Lakes Research	Miami Lakes	Florida
United States	Bon Secours Virginia Breast Center	Midlothian	Virginia
United States	Columbia St. Marys Cancer Center	Milwaukee	Wisconsin
United States	Community Hospital of Monterey Peninsula	Monterey	California
United States	Coastal Carolina Breast Center	Murrells Inlet	South Carolina
United States	Nashville Breast Center	Nashville	Tennessee
United States	Alta Bates	Oakland	California
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	University of Nebraska	Omaha	Nebraska
United States	Comprehensive Cancer Center - Palm Springs	Palm Springs	California
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	St. Clair Hospital	Pittsburgh	Pennsylvania
United States	Sutter Roseville Medical Center	Roseville	California
United States	Christian Hospital	Saint Louis	Missouri
United States	Kathryn A. Wagner Private Practice	San Antonio	Texas
United States	Radiation Oncology of San Antonio	San Antonio	Texas
United States	SHARP Memorial	San Diego	California
United States	Redwood Regional	Santa Rosa	California
United States	Center for Breast Care	Savannah	Georgia
United States	21 Century Oncology	Scottsdale	Arizona
United States	Swedish Cancer Institute	Seattle	Washington
United States	Willis-Knighton Cancer Center	Shreveport	Louisiana
United States	Hematology/Oncology of The North Shore	Skokie	Illinois
United States	Northern Indiana Cancer Research	South Bend	Indiana
United States	Providence Cancer Institute	Southfield	Michigan
United States	Rockwood Clinic	Spokane	Washington
United States	Stamford Hospital	Stamford	Connecticut
United States	University of Toledo	Toledo	Ohio
United States	Waukesha Memorial Hospital	Waukesha	Wisconsin
United States	Wheaton Franciscan Healthcare	Wauwatosa	Wisconsin
United States	Wellness Oncology Hematology	West Hills	California
United States	Wellness Oncology Hematology	West Hills	California
United States	Virtua Health	Willingboro	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Agendia

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chemosensitivity as defined by pCR	For neo-adjuvant chemotherapy patients the primary endpoint is pathological complete response (pCR) which is defined as the absence of invasive carcinoma in both the breast and axilla at microscopic examination of the resection specimen, regardless of the presence of carcinoma in situ. The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test.	Up to 6 months
Primary	Endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1)	The primary endpoint for patients with neo-adjuvant hormonal therapy is partial response which is defined as decrease in longest tumor diameter. The response rate and corresponding confidence intervals will be presented as a proportion of all patients enrolled. Comparison of response rates between different molecular subgroups will be conducted using Pearson Chi-square test.	Up to 6 months
Secondary	Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results.	Correlation of chemosensitivity and endocrine sensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results will be determined using Pearson correlation and linear fit models.	Up to 6 months.
Secondary	Assess metastasis-free survival and relapse-free survival in molecular subgroups, determined by the established MammaPrint, BluePrint, profiles.	Kaplan-Meier curves for DMFS will be calculated for the following eight subgroups; Luminal subtype; ERBB2 subtype; Basal subtype; Luminal subtype and high risk MammaPrint; Luminal subtype and low risk MammaPrint; ERBB2 subtype and high risk MammaPrint; ERBB2 subtype and low risk MammaPrint	At -2-3 years and 5 years after definitive surgery.
Secondary	Compare local IHC and FISH results (if available) with TargetPrint results.	Correlation of TargetPrint ER, PR, and HER2 microarray readout with IHC/FISH assessment will be determined using Pearson correlation and linear fit models. Agreement measurements between binary microarray and IHC classifications will be based on 2-way contingency table analysis and include overall concordance, positive agreement defined as the number of samples classified positive by both IHC and TargetPrint divided by the number of positive samples using IHC, negative agreement and Cohen's Kappa coefficient score.	Baseline; before start of neo-adjuvant therapy.
Secondary	Compare the three BluePrint molecular subgroups with IHC-based subtype classification.	Correlation of BluePrint molecular subgroup microarray readout with IHC-based subtype classification.	Baseline; before start of neo-adjuvant therapy.
Secondary	Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision.	Review the impact of MammaPrint, TargetPrint, and BluePrint on physician treatment decisions.	Baseline; before start neo-adjuvant therapy.