NBRST: Prospective Neo-adjuvant REGISTRY Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Agendia
Sponsor:
Information provided by (Responsible Party):
Agendia
ClinicalTrials.gov Identifier:
NCT01479101
First received: November 18, 2011
Last updated: July 31, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention
Breast Cancer
Other: MammaPrint 70-gene expression profile
Other: BluePrint 80 gene expression profile

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Prospective Neo-adjuvant REGISTRY Trial Linking MammaPrint, Subtyping and Treatment Response: Neoadjuvant Breast Registry - Symphony Trial (NBRST) (Pronounced "in Breast")

Resource links provided by NLM:


Further study details as provided by Agendia:

Primary Outcome Measures:
  • Chemosensitivity as defined by pCR [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Correlate chemosensitivity (as defined by pCR) to TheraPrint Therapy Gene Assay results. [ Time Frame: Up to 6 months. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]

    Kaplan-Meier curves for DMFS will be calculated for the following eight subgroups

    1. Luminal subtype
    2. ERBB2 subtype
    3. Basal subtype
    4. Luminal subtype and high risk MammaPrint
    5. Luminal subtype and low risk MammaPrint
    6. ERBB2 subtype and high risk MammaPrint
    7. 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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
  • Document impact of MammaPrint, TargetPrint and BluePrint result on treatment decision. [ Time Frame: Baseline; before start neo-adjuvant therapy. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

As part of routine breast cancer treatment, the doctor will conduct a core needle biopsy and provide tissue from the tumor to Agendia for testing. After the diagnostic test(s) from the Agendia Breast Cancer Suite have been performed on the tumor specimen, there might be some remaining tissue left.


Estimated Enrollment: 1000
Study Start Date: July 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01479101

Contacts
Contact: Sarah Untch, MS 4127706906 sarah.untch@agendia.com
Contact: Lisette Stork, MSc lisette.stork@agendia.com

  Show 78 Study Locations
Sponsors and Collaborators
Agendia
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Agendia
ClinicalTrials.gov Identifier: NCT01479101     History of Changes
Other Study ID Numbers: P0339 NBRST Registry
Study First Received: November 18, 2011
Last Updated: July 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Agendia:
neo adjuvant, breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on August 21, 2014