Presentation on theme: "MINT study Principal Investigator: Charles E. Cox, M.D."— Presentation transcript:
1MINT study Principal Investigator: Charles E. Cox, M.D. Co Investigators: Stefan Glück, M.D.
2MINTMINT I: Multi-Institutional Neo-adjuvant Therapy MammaPrint Project IPrincipal Investigator: Charles E. Cox, M.D. USF, Tampa FLCo Investigator: Stefan Glück, M.D. UM/Sylvester Comprehensive Cancer Center University of Miami, Miller School of Medicine FLTotal of 226 patients; up to 10 institutes in the USFull genome gene expression profiling Agendia IncCentral pathology review at USF pathology FLTimelines; Oct Oct 2013
3Breast Cancer Symphony Suite MammaPrint: 70-gene profile prognostic and predictive tumor analysisWill patient benefit from chemotherapy?TargetPrint: Gene expression of ER/PR/HER 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
4pCR rate of MammaPrint and BluePrint in previous neo-adjuvant studies
5MINT; 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.
6MINT; Eligibility Criteria Inclusion criteria:Women with histologically proven invasive breast cancer; T2(≥3.5cm)-T4, N0,M0 or T2-4N1M0DCIS or LCIS are allowed in addition to invasive cancer at T2 or T3 level.Age ≥ 18 years.Measurable disease in two dimensionsAdequate bone marrow reserves, adequate renal function, and hepatic functionSigned informed consentExclusion criteriaPatients 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.
8Study Design Flowchart Central slide pathology reviewPatient information & informed consentCore NeedleBiopsiesTACSurgery including nodal stagingHER2-Sample placed in RNA Retain, send to AgendiaFull Genome Array* successfulTCHER2-Central slide pathology reviewddAC/FEC100,paclitaxel or docetaxelHER2-TCHHER2+Full Genome Array* not successfulT H/FEC HHER2+CRF 1baselineCRF 2surgeryPatient ineligible* (Including diagnostic commercial testing for Symphony Breast cancer Suite)
9Neo-adjuvant therapy For HER2 negative patients: TAC chemotherapy TC chemotherapyDose Dense AC or FEC100 followed by paclitaxel or docetaxel chemotherapyFor HER2 positive patients:TCH chemotherapyT H followed by FEC HDose adjustmentsHematological and non-hematological toxicities should be managed by treating oncologist as per routine clinical practice.
10Future Research – Remaining Tissue Agendia will store remaining tissue from patient samplesThis tissue can be used for future scientific researchPatients are asked in the patient consent form to provide consent for storage and future researchPlease 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
11Tissue CollectionTissue 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 coresIf a 11 gauge needle is used: 4 coresIf a 9 gauge needle is used: 3 cores
12Sending 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.
13Central Pathology Review Central pathology review for RCB score will be done at USF Pathology FLRepresentative 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 33612Lisette to review and adjust as needed
14Procedures for Sending Slides APPENDIX III Pathology Worksheet for Core/Incisional BiopsyPlease send the following, and complete the form below:One H&E section of tumorER immunohistochemical stainPR immunohistochemical stainHER2 immunohistochemical stain or FISH/CISH/SISH report10 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. Lateralitya. Left breastb. Right breast2. Locationa. UOQb. LOQc. UIQd. LIQ3. Time in formalina. ≥ 6 to ≤ 48 hoursb. Other
15Procedures for Sending Slides APPENDIX IV Pathology Worksheet for Post-Neoadjuvant SpecimensPlease send the following, and complete the form below:Two representative blocks of tumor, or 15 unstained slides on positively charged glass slidesCopy of final pathology report (including gross description)1. Specimena. Lumpectomy/partial mastectomyb. Total mastectomyc. Skin-sparing, nipple-sparing total mastectomyd. Nipple-sparing total mastectomye. Modified radical mastectomyf. Other2. Residual tumora. Grossly identifiedi. Dimensions: ____ x ____ x ____ cmii. Percent gross necrosis:b. Not grossly identified *Fibrotic tumor bed dimensions: ____ x ____ x ____ cmDistance from closest margin: ____*NOTE: If no definitive tumor grossly identified, please submit entire tumor bed sequentially
16Pathology GuidelinesNote: additional guidelines for your pathology are outlined in Appendix II of the protocol.
17Clinical Report Form Web based data collection/electronic CRF CRF1; Baseline informationCRF2; After surgeryRelatively easy to complete compared to drug trial15-20 minutes for CRF1 and 2
18Accessing the Database There is one hyperlink to access all the electronic Case Report Forms (CRFs) https://trials.agendia.com/MINTYou will receive an institution specific site number and password from your Agendia Clinical Research Manager.Institution:
19CRF 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.
20CRF 1: Questions Pathology Date of histologic diagnosis Histopathologic tumor type Histological gradeER, PR and Her2-neu statusVascular invasionTNMNodal stagingDate nodal stagingIf sentinel lymph node Number of sentinel nodes removed Number of countsBlue dyeHistology of SLN: Concordance of nodal histology to primary tumorBaseline Patient characteristicsAge at diagnosisEthnicity/ originMenopausal status Date of biopsySpecimen typeTumor measurementsKind of imaging usedPrimary tumor sizeSize largest metastatic lymph node
21CRF 2: Questions Sentinel Lymph Node Procedure (SLNP) If yes Neo-adjuvant treatmentRegimen given Was specified number of cycles completed?Any grade 4 or 5 CTC for Adverse Events observed?Surgery informationDate breast carcinoma surgeryType of surgeryLymph node assessmentsPathologyNodal statusypTNTumor measurementsWhat kind of imaging has been used ?Primary tumor sizeSize largest metastatic lymph nodeTreatment responseLymph node assessmentsSentinel Lymph Node Procedure (SLNP) If yesNumber of sentinel nodes examinedNumber of positive sentinel nodesNumber of negative sentinel nodesBlue dyeConcordance of nodal histology to primary tumor Axillary Lymph Node Dissection (ALND) If yesNumber of axillary nodes examinedNumber of positive axillary nodesNumber of negative axillary nodesSLNP and ALND if yes:
22Contacts:Jessica Gibson, Clinical Research Manager (619)