Informatics in Breast Cancer ResearchI-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.

ON

STUDY

MRIBiopsy

Blood DrawMUGA/ECHO

CT/PET

Screening

RANDOMIZE

Consent #2Treatment Consent

Consent #1

S

U

R

G

E

R

Y

Tissue

Paclitaxel* +Investigational Agent C AC

MRIBiopsy

Blood Draw

MRIBlood Draw

MRIBlood 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

ON

STUDY

MRIBiopsy

Blood DrawMUGA/ECHO

CT/PET

Screening

RANDOMIZE

Consent #2Treatment Consent

Consent #1

S

U

R

G

E

R

Y

Tissue

Paclitaxel* +Investigational Agent C AC

MRIBiopsy

Blood Draw

MRIBlood Draw

MRIBlood 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 TRIALInformatics 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

TRANSCEND - Systems OverviewTolven eCHR

Data Coordinating

Center

Study SitesCase Report

Forms

Agendia

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 • Email alerts to when a CRF is

ready for review & verification

• Email 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 TRIAL2TRANSCEND - 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