NBRST: Prospective Neo-adjuvant REGISTRY Trial (NBRST)
|ClinicalTrials.gov Identifier: NCT01479101|
Recruitment Status : Active, not recruiting
First Posted : November 24, 2011
Last Update Posted : November 2, 2016
|Condition or disease||Intervention/treatment|
|Breast Cancer||Other: MammaPrint 70-gene expression profile Other: BluePrint 80 gene expression profile|
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.
- 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.
|Study Type :||Observational|
|Actual Enrollment :||1142 participants|
|Official Title:||Prospective Neo-adjuvant REGISTRY Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry - Symphony Trial (NBRST) (Pronounced "in Breast")|
|Study Start Date :||July 2011|
|Actual Primary Completion Date :||January 2015|
|Estimated Study Completion Date :||January 2020|
MammaPrint, BluePrint, neo-adj CT or HT
All patients receive the MammaPrint and BluePrint gene expression profile. Treatment at the discretion of the physician while adhering to NCCN guidelines.
|Other: MammaPrint 70-gene expression profile Other: BluePrint 80 gene expression profile|
- Chemosensitivity as defined by pCR [ Time Frame: Up to 6 months ]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.
- Endocrine sensitivity as defined by partial response (decrease in longest tumor diameter or residual cancer burden category 1 (RCB1) [ Time Frame: Up to 6 months ]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.
- Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results. [ Time Frame: Up to 6 months. ]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.
- Assess metastasis-free survival and relapse-free survival in molecular subgroups, determined by the established MammaPrint, BluePrint, profiles. [ Time Frame: At -2-3 years and 5 years after definitive surgery. ]
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
- Compare local IHC and FISH results (if available) with TargetPrint results. [ Time Frame: Baseline; before start of neo-adjuvant therapy. ]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.
- Compare the three BluePrint molecular subgroups with IHC-based subtype classification. [ Time Frame: Baseline; before start of neo-adjuvant therapy. ]
- Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision. [ Time Frame: Baseline; before start neo-adjuvant therapy. ]
Biospecimen Retention: Samples With DNA
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01479101
Show 77 Study Locations
|Principal Investigator:||Pat Whitworth, MD||Nashville Breast Center|
|Principal Investigator:||Stephanie Akbari, MD||Reinsch Pierce Family Center for Breast Health|
|Principal Investigator:||Mark Gittleman, MD||Breast Care Specialists|
|Principal Investigator:||Peter Beitsch, MD||Dallas Surgical Group|