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MINT study

MINT study. Principal Investigator : Charles E. Cox, M.D. Co Investigators: Stefan Glück , M.D. . MINT. MINT I: M ulti- I nstitutional N eo-adjuvant T herapy MammaPrint Project I Principal Investigator : Charles E. Cox, M.D. USF, Tampa FL

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MINT study

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  1. MINT study Principal Investigator: Charles E. Cox, M.D. Co Investigators: Stefan Glück, M.D.

  2. 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

  3. Breast Cancer Symphony Suite MammaPrint: 70-gene profile prognostic and predictive tumor analysis Will patient benefit from chemotherapy? TargetPrint: Gene expression of ER/PR/HER2 Centralized lab confirmation of receptor status Will patient benefit from hormonal treatment? BluePrint: 80-gene molecular subtyping profile Basal, Luminal, and HER2 subtypes Which therapy works best? TheraPrint: Gene expression of 56 genes Potential markers for prognosis and therapeutic response Potential therapy options saved for the future

  4. pCR rate of MammaPrint and BluePrint in previous neo-adjuvant studies

  5. MINT; Study Objectives • To determine the predictive power of chemosensitivityof the combination ofMammaPrint and BluePrintas measured by pCR. • To compare TargetPrintsingle 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 andchemoresponsiveness. • To compare the three BluePrintmolecular subtype categories with IHC-based subtype classification.

  6. 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.

  7. MINT; Nodal staging

  8. Study Design Flowchart Central slide pathology review Patient information & informed consent Core Needle Biopsies TAC Surgery including nodal staging HER2- Sample placed in RNA Retain, send to Agendia Full Genome Array* successful TC HER2- Central slide pathology review ddAC/FEC100, paclitaxel or docetaxel HER2- TCH HER2+ Full Genome Array* not successful T H/FEC H HER2+ CRF 1 baseline CRF 2 surgery Patient ineligible * (Including diagnostic commercial testing for Symphony Breast cancer Suite)

  9. Neo-adjuvant therapy For HER2 negative patients: • TAC chemotherapy • TC chemotherapy • Dose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapy For 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.

  10. Future Research – Remaining Tissue • 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

  11. 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   

  12. Sending Sample to Agendia • Remove large specimen tube from kit and open it. • Place large screw cap with small specimen vial on table and open small specimen vial. • Place a barcode label from the completed requisition form on to the vial. • Place the small specimen vial into the large specimen tube and place the tube into the specimen safety bag. • 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. • Package the kit into the FedEx shipping pack and attach the pre printed label for shipment to Agendia Inc. • Please call Fed Ex for pickup.

  13. 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 Pathology Attn: MINT Trial 12901 Bruce B. Downs Blvd MDC 11 Tampa, FL 33612

  14. Procedures for Sending Slides APPENDIX 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

  15. Procedures for Sending Slides APPENDIX 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 * • Fibrotic tumor bed dimensions: ____ x ____ x ____ cm • Distance from closest margin: ____ *NOTE: If no definitive tumor grossly identified, please submit entire tumor bed sequentially

  16. Pathology Guidelines • Note: additional guidelines for your pathology are outlined in Appendix II of the protocol.

  17. 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

  18. 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:

  19. CRF Overview Administrative page Detailed Data Entry Instructions will be sent to site. Samples will appear in the database if they are found to be eligible.

  20. 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 • Histopathologictumor 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

  21. CRF 2: Questions • 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: Neo-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

  22. Contacts: • Jessica Gibson, Clinical Research Manager (619)316-1416 jessica.gibson@agendia.com

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