Informatics in Breast Cancer Research I-SPY 2 TRIAL & TRANSCEND

I-SPY 2 TRIAL Screen phase 2 agents in combination with standard chemotherapy in neoadjuvant setting –Endpoint is pCR –Intermediate endpoint is MRI Volume Accelerate process of identifying drugs that are effective for specific breast cancer subtypes –Integration of biomarkers Reduce the cost, time, and number of patients needed to get effective drugs to market –“threshold” is 85% predicted likelihood of success in a 300-patient phase 3 trial for drug-biomarker pair Design goals of I-SPY 2

I-SPY 2 TRIAL I-SPY 2 Adaptive Trial Design *HER2 positive participants will also receive Trastuzumab. An investigational agent may be used instead of Trastuzumab. ONSTUDYONSTUDY MRI Biopsy Blood Draw MUGA/ECHO CT/PET Screening RANDOMIZERANDOMIZE Consent #2 Treatment Consent Consent #1 SURGERYSURGERY Tissue Paclitaxel* + Investigational Agent C AC MRI Biopsy Blood Draw MRI Blood Draw MRI Blood Draw Paclitaxel* + Investigational Agent D AC Paclitaxel* + Investigational Agent E AC Paclitaxel* + Investigational Agent B AC Paclitaxel* + Investigational Agent A AC Paclitaxel* AC

I-SPY 2 TRIAL I-SPY 2 Adaptive Trial Design ONSTUDYONSTUDY MRI Biopsy Blood Draw MUGA/ECHO CT/PET Screening RANDOMIZERANDOMIZE Consent #2 Treatment Consent Consent #1 SURGERYSURGERY Tissue Paclitaxel* + Investigational Agent C AC MRI Biopsy Blood Draw MRI Blood Draw MRI Blood Draw *HER2 positive participants will also receive Trastuzumab. An investigational agent may be used instead of Trastuzumab. Paclitaxel* + Investigational Agent D AC Paclitaxel* + Investigational Agent E AC Paclitaxel* + Investigational Agent B AC Paclitaxel* + Investigational Agent A AC Paclitaxel* AC Paclitaxel* + Investigational Agent FG AC

I-SPY 2 TRIAL Informatics Needs for Adaptive Clinical Trials – I-SPY 2 Manage information across multiple sites Data gathering must be closely monitored as the trial depends on rapid eligibility determination and therapeutic intervention - do not want to delay therapy Randomization as a web service (automated - but with review) Combining evaluation of drugs and biomarkers together –Biomarker data is of various types (arrays, imaging volume, numeric scales, etc..) Scientists need access to data early and in an integrated fashion (one stop shopping)

I-SPY 2 TRIAL What is TRANSCEND? TRANslational Informatics System to Coordinate Emerging Biomarkers, Novel Agents, and Clinical Data An IT Bundle to Support Adaptive Trials with Novel Agents and Emerging Biomarkers

I-SPY 2 TRIAL TRANSCEND Objectives Develop an information management infrastructure to support adaptive clinical trials like I-SPY 2 Provide real-time data verification for more efficient analysis of trial data Provide a demonstration of caBIG  infrastructure in use in a large multi-center trial Demonstrate integration of a clinical system (electronic health record system) with a clinical research infrastructure

I-SPY 2 TRIAL Tolven eCHR Data Coordinating Center Study Sites Case Report Forms Study Sites Case Report Forms Agendia  Integration Hub (caXchange) Integration Hub (caXchange) caTissue Suite caIntegrator caAers caArray Research Labs MD Anderson Randomization Engine Automated interface Manual interface

I-SPY 2 TRIAL TRANSCEND – eCHR Data Collection

I-SPY 2 TRIAL Electronic copy of source documentation with each CRF Easy to complete case report forms with smart logic TRANSCEND – eCHR Data Collection

I-SPY 2 TRIAL TRANSCEND – eCHR Data Verification Real-time data review and verification Instant submission of CRF with source documentation to Data Coordination Center

I-SPY 2 TRIAL TRANSCEND – eCHR Data Collection alerts to when a CRF is ready for review & verification alerts when a CRF is rejected by the DCC

I-SPY 2 TRIAL TRANSCEND - Randomization

I-SPY 2 TRIAL Future Direction with 2TRANSCEND Integrate additional platforms Web-based Patient Communication and Care Plan –Aids in decision making about participating in a clinical trial as well as enabling study staff to communicate with patient’s regarding study appointments Web interface allowing patients to directly input: –Adherence to treatment regimens –Adverse events (PRO-CTCAE) –Follow-up information Adopt Annotation Imaging Mark-up (AIM) tool to enable researches ability to centrally review and analyze images

I-SPY 2 TRIAL 2TRANSCEND - Integrated Systems

I-SPY 2 TRIAL Dr. Laura Esserman – I-SPY TRIAL, TRANSCEND PI (UCSF) Dr. Michael Hogarth - TRANSCEND Technical Director (UC Davis) Meg Young – TRANSCEND Project Manager (UCSF) Sarah Davis – I-SPY 2 TRIAL Manager (UCSF) –Joyce Lee, Julia Lyandres (software testing, quality control) Sorena Nadaf – Informatics Design (UCSF) Dr. Angela DeMichele – Clinical Oncology (UPenn) Don Berry & Kyle Wathen – Randomization Engine (MDACC) John Churin – Software Lead Engineer (Tolven) Ashwin Koleth – Software Development (Cyrus-XP) John Koisch – Architecture (NCI) Kathy Hajopoulos – Project Oversight (UCSF) Nancy Roche – Project Oversight (SAIC) TRANSCEND TEAM TRANSCEND development funded by the National Cancer Institute (NCI), Subcontract # 28XS197

I-SPY 2 TRIAL Dr. Laura Esserman – I-SPY TRIAL, 2TRANSCEND PI (UCSF) Dr. Michael Hogarth - 2TRANSCEND Technical Director (UC Davis) Sarah Davis– 2TRANSCEND Project Manager (UCSF) Meredith Buxton – I-SPY 2 Program Director (UCSF) Dr. Angela DeMichele – Clinical Oncology (UPenn) Don Berry & Kyle Wathen – Randomization Engine (MDACC) John Churin – Software Lead Engineer (Tolven) Ashwin Koleth – Software Development (Cyrus-XP) Eve Shalley – Project Manager (NCI) Santosh Joshi & CBIIT caCIS Team (NCI) Ian Fore & CBIIT caTissue Team (NCI) Paul Baumgarnter & CBIIT caAERS Team (NCI) Juli Klemm & CBIIT caArray Team (NCI) Shine Jacob & CBIIT caIntegrator Team (NCI) Robert Shirley & CBIIT Architechture Team (NCI) 2TRANSCEND TEAM 2TRANSCEND development funded by the National Cancer Institute (NCI), Agreement No. 12ST1002