Overview MINT Study Presentation

Report
MINT study
Principal Investigator: Charles E. Cox, M.D.
Co Investigators: Stefan Glück, M.D.
MINT
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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
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
pCR rate of MammaPrint and BluePrint in
previous neo-adjuvant studies
MINT; Study Objectives
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To determine the predictive power of chemosensitivity of the
combination of MammaPrint and BluePrint as measured by pCR.
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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.
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To identify and/or validate predictive gene expression profiles of clinical
response/resistance to chemotherapy.
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To identify possible correlations between the TheraPrint Research Gene
Panel outcomes and chemoresponsiveness.
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To compare the three BluePrint molecular subtype categories with IHCbased subtype classification.
MINT; Eligibility Criteria
Inclusion criteria:
• Women with histologically proven invasive breast cancer; T2(≥3.5cm)-T4,
N0,M0 or T2-4N1M0
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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
Full
Genome
Array* not
successful
HER2-
Full
Genome
Array*
successful
TAC
TC
HER2-
Sample
placed in
RNA
Retain,
send to
Agendia
Central
slide
pathology
review
ddAC/FEC100,
paclitaxel or docetaxel
HER2+
Core
Needle
Biopsies
TCH
HER2+
Patient
information
& informed
consent
HER2-
Study Design Flowchart
T H/FEC H
CRF
1
baseline
Patient
ineligible
* (Including diagnostic commercial testing for Symphony Breast cancer Suite)
Surgery
including
nodal
staging
Central
slide
pathology
review
CRF
2
surgery
Neo-adjuvant therapy
For HER2 negative patients:
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TAC chemotherapy
TC chemotherapy
Dose Dense AC or FEC100 followed by paclitaxel or docetaxel
chemotherapy
For HER2 positive patients:
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TCH chemotherapy
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T H followed by FEC H
Dose adjustments
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Hematological and non-hematological toxicities should be managed
by treating oncologist as per routine clinical practice.
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
Tissue Collection
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Tissue should be collected by incisional biopsy (when placing port)
or via core needle biopsy.
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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.
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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.
B.
C.
D.
E.
F.
G.
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.
Central Pathology Review
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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
Procedures for Sending Slides
APPENDIX III Pathology Worksheet for Core/Incisional Biopsy
Please send the following, and complete the form below:
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One H&E section of tumor
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ER immunohistochemical stain
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PR immunohistochemical stain
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HER2 immunohistochemical stain or FISH/CISH/SISH report
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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 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 *
i.
c.
Fibrotic tumor bed dimensions: ____ x ____ x ____ cm
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:
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.
CRF 1: Questions
Pathology
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
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Date of histologic diagnosis
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Histopathologic tumor type
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Histological grade
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ER, PR and Her2-neu status
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Vascular invasion
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TNM
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Nodal staging
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Date nodal staging
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If sentinel lymph node
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Number of sentinel nodes removed
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Number of counts
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Blue dye
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Histology of SLN:
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Concordance of nodal histology to
primary tumor
CRF 2: Questions
Neo-adjuvant treatment
Lymph node assessments
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Regimen given
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Sentinel Lymph Node Procedure (SLNP) If yes
Was specified number of cycles
completed?
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Any grade 4 or 5 CTC for Adverse
Events observed?
Surgery information
•Number of sentinel nodes examined
•Number of positive sentinel nodes
•Number of negative sentinel nodes
•Blue dye
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Date breast carcinoma surgery
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Type of surgery
•Concordance
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Lymph node assessments
tumor
Pathology
 Nodal status
 ypTN
of nodal histology to primary
Axillary Lymph Node Dissection (ALND) If yes
•Number of axillary nodes examined
Tumor measurements
•Number of positive axillary nodes
 What kind of imaging has been used ?
•Number of negative axillary nodes
 Primary tumor size
SLNP and ALND if yes:
 Size largest metastatic lymph node
 Treatment response
Contacts:
• Jessica Gibson, Clinical Research
Manager (619)316-1416
[email protected]

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