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MINT study
Principal Investigator: Charles E. Cox, M.D.
Co Investigators: Stefan Glück, M.D.
MINT
• MINT I: Multi-Institutional Neo-adjuvant Therapy MammaPrint Project I
• Principal Investigator: Charles E. Cox, M.D. USF, Tampa FL• Co Investigator: Stefan Glück, M.D. UM/Sylvester
Comprehensive Cancer Center University of Miami, Miller School of Medicine FL
• Total of 226 patients; up to 10 institutes in the US• Full genome gene expression profiling Agendia Inc• Central pathology review at USF pathology FL• Timelines; Oct 2011- Oct 2013
MammaPrint: 70-gene profile prognostic and predictive tumor
analysisWill patient benefit from chemotherapy?TargetPrint: Gene expression of ER/PR/HER2
Centralized lab confirmation of receptor statusWill patient benefit from hormonal treatment?BluePrint: 80-gene molecular subtyping profile
Basal, Luminal, and HER2 subtypesWhich therapy works best?
TheraPrint: Gene expression of 56 genes Potential markers for prognosis and therapeutic responsePotential therapy options saved for the future
Breast Cancer Symphony Suite
pCR rate of MammaPrint and BluePrint in previous neo-adjuvant studies
MINT; Study Objectives
• To determine the predictive power of chemosensitivity of the combination of MammaPrint and BluePrint as measured by pCR.
• To compare TargetPrint single gene read out of ER, PR and HER2 with local and centralized IHC and/or CISH/FISH assessment of ER, PR and HER2.
• To identify and/or validate predictive gene expression profiles of clinical response/resistance to chemotherapy.
• To identify possible correlations between the TheraPrint Research Gene Panel outcomes and chemoresponsiveness.
• To compare the three BluePrint molecular subtype categories with IHC-based subtype classification.
MINT; Eligibility Criteria
Inclusion criteria:• Women with histologically proven invasive breast cancer;
T2(≥3.5cm)-T4, N0,M0 or T2-4N1M0• DCIS or LCIS are allowed in addition to invasive cancer at T2 or T3
level.• Age ≥ 18 years.• Measurable disease in two dimensions • Adequate bone marrow reserves, adequate renal function, and
hepatic function • Signed informed consent Exclusion criteria• Patients with inflammatory breast cancer.• 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 inter current infections, or other serious
uncontrolled concomitant disease.
MINT; Nodal staging
Study Design Flowchart
Core Needle Biopsies
Sample placed in
RNA Retain, send to Agendia
Full Genome Array*
not successfu
l
Patient ineligible
Patient informati
on & informed consent
TAC
CRF 1
baseline
Surgery including nodal staging
CRF 2
surgery
* (Including diagnostic commercial testing for Symphony Breast cancer Suite)
Central slide
pathology review
Central slide
pathology review
TC
ddAC/FEC100, paclitaxel or
docetaxel
TCH
Full Genome Array*
successful
HER
2-
HER
2-
HER
2-
HER
2+
T H/FEC HH
ER
2+
Neo-adjuvant therapy
For HER2 negative patients:• TAC chemotherapy• TC chemotherapy• Dose Dense AC or FEC100 followed by paclitaxel or
docetaxel chemotherapyFor HER2 positive patients:• TCH chemotherapy• T H followed by FEC H
Dose adjustments• Hematological and non-hematological toxicities should be
managed by treating oncologist as per routine clinical practice.
• Agendia will store remaining tissue from patient samples
• This tissue can be used for future scientific research
• Patients are asked in the patient consent form to provide consent for storage and future research
• Please note: If a patient does not wish to allow their tissue to be used for future research, it is the responsibility of the site to communicate this with Agendia
Future Research – Remaining Tissue
Tissue Collection
• Tissue should be collected by incisional biopsy (when placing port) or via core needle biopsy.
• If the tissue is obtained by incisional biopsy then the tissue sample should be no greater than 3 to 4 mm in thickness and between 8 to 10 mm in diameter.
• Core needle biopsies should be obtained with a 14 gauge or larger needle.
– If a 14 gauge needle is used: 5 cores
– If a 11 gauge needle is used: 4 cores
– If a 9 gauge needle is used: 3 cores
Sending Sample to Agendia
A. Remove large specimen tube from kit and open it.
B. Place large screw cap with small specimen vial on table and open small specimen vial.
C. Place a barcode label from the completed requisition form on to the vial.
D. Place the small specimen vial into the large specimen tube and place the tube into the specimen safety bag.
E. Place the sealed specimen bag into the shipping kit along with the requisition form. IMPORTANT: ensure that the study sticker is affixed to the requisition form.
F. Package the kit into the FedEx shipping pack and attach the pre printed label for shipment to Agendia Inc.
G. Please call Fed Ex for pickup.
Central Pathology Review
• Central pathology review for RCB score will be done at USF Pathology FL
• Representative slides of core needle biopsy, sentinel lymph node biopsies and surgical sample should be send to:
USF PathologyAttn: MINT Trial12901 Bruce B. Downs Blvd MDC 11Tampa, FL 33612
Procedures for Sending SlidesAPPENDIX III Pathology Worksheet for Core/Incisional Biopsy
Please send the following, and complete the form below: • One H&E section of tumor • ER immunohistochemical stain • PR immunohistochemical stain • HER2 immunohistochemical stain or FISH/CISH/SISH report • 10 unstained sections on positively-charged glass slides (If ER, PR, and/or HER2 studies not available, please send an additional 10 unstained sections on
positively-charged glass slides)
Questions to be completed on worksheet:1. Laterality
a. Left breast b. Right breast
2. Location a. UOQ b. LOQ c. UIQ d. LIQ
3. Time in formalin a. ≥ 6 to ≤ 48 hours b. Other
Procedures for Sending SlidesAPPENDIX IV Pathology Worksheet for Post-Neoadjuvant Specimens
Please send the following, and complete the form below: • Two representative blocks of tumor, or 15 unstained slides on positively
charged glass slides • Copy of final pathology report (including gross description) 1. Specimen
a. Lumpectomy/partial mastectomy b. Total mastectomy c. Skin-sparing, nipple-sparing total mastectomy d. Nipple-sparing total mastectomy e. Modified radical mastectomy f. Other
2. Residual tumor a. Grossly identified
i. Dimensions: ____ x ____ x ____ cm ii. Percent gross necrosis:
b. Not grossly identified *i. Fibrotic tumor bed dimensions: ____ x ____ x ____ cm
c. Distance from closest margin: ____
*NOTE: If no definitive tumor grossly identified, please submit entire tumor bed sequentially
Pathology Guidelines
• Note: additional guidelines for your pathology are outlined in Appendix II of the protocol.
Clinical Report Form
• Web based data collection/electronic CRF– CRF1; Baseline information– CRF2; After surgery
Relatively easy to complete compared to drug trial
15-20 minutes for CRF1 and 2
Accessing the Database◦ There is one hyperlink to access all the electronic Case Report Forms (CRFs)
https://trials.agendia.com/MINT
◦ You will receive an institution specific site number and password from your Agendia
Clinical Research Manager.
Institution:
Detailed Data Entry Instructions will be sent to site.
Samples will appear in the database if they are found to be eligible.
CRF Overview Administrative page
CRF 1: Questions
Baseline Patient characteristics• Age at diagnosis• Ethnicity/ origin• Menopausal status • Date of biopsy• Specimen type
Tumor measurements• Kind of imaging used • Primary tumor size• Size largest metastatic lymph node
Pathology Date of histologic diagnosis Histopathologic tumor type Histological grade ER, PR and Her2-neu status Vascular invasion TNM Nodal staging Date nodal staging If sentinel lymph node
Number of sentinel nodes removed Number of counts Blue dye Histology of SLN: Concordance of nodal histology to
primary tumor
CRF 2: QuestionsNeo-adjuvant treatment
• Regimen given
• Was specified number of cycles completed?
• Any grade 4 or 5 CTC for Adverse Events observed?
Surgery information
• Date breast carcinoma surgery
• Type of surgery
• Lymph node assessments
Pathology
Nodal status
ypTN
Tumor measurements
What kind of imaging has been used ?
Primary tumor size
Size largest metastatic lymph node
Treatment response
Lymph node assessments
Sentinel Lymph Node Procedure (SLNP) If yes
•Number of sentinel nodes examined
•Number of positive sentinel nodes
•Number of negative sentinel nodes
•Blue dye
•Concordance of nodal histology to primary tumor
Axillary Lymph Node Dissection (ALND) If yes
•Number of axillary nodes examined
•Number of positive axillary nodes
•Number of negative axillary nodes
SLNP and ALND if yes:
