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