The Biomarkers Consortium

I-SPY 2: Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis

The I-SPY 2 trial employs a groundbreaking clinical trial model that uses genetic or biological markers (“biomarkers”) from individual patients’ tumors to screen promising new treatments, identifying which treatments are most effective in specific types of patients. In addition, an innovative adaptive trial design will enable researchers to use early data from one set of patients to guide decisions about which treatments might be more useful for patients later in the trial, and eliminate ineffective treatments more quickly. The large-scale trial involves a unique collaboration by scientists from the National Cancer Institute (NCI), FDA, and nearly 20 major cancer research centers across the country. Study results will be made broadly available to the entire cancer research and development community. 

The trial was announced at a press conference held at the National Press Club on March 17, 2010.

The Biomarkers Consortium: I-SPY 2 Press Conference from Foundation for the the NIH on Vimeo.

NBC 4 reported on the unique promise of the clinical trial.

NBC 4 Report: I-SPY 2 Clinical Trial from Foundation for the NIH on Vimeo.

A Groundbreaking Clinical Trial

I-SPY 2 has the potential to significantly reduce the cost of drug development and speed the process of screening drugs with the goal of bringing safe and effective new drugs to market more efficiently. Currently, it takes over $1 billion, 12 to 15 years, and thousands of patient volunteers to get a single drug to market. I-SPY 2 was developed to allow the activity of drugs to be assessed much earlier in the research process, potentially enabling drugs to be developed and approved using fewer patients, less time and far fewer resources. The goal is to shave several years and hundreds of millions of dollars off the current process. 

The I-SPY 2 trial will focus on treatment in the neoadjuvant therapy setting, in which chemotherapy is given to patients to reduce tumor size before surgery. Imaging results throughout this chemotherapy period will measure whether the treatment is working. All patients will receive the current standard of care and most participants will receive one investigational drug. A distinctive feature of the trial is that it will screen multiple drugs from multiple companies—up to 12 different cancer drugs over the course of the trial.

Five new investigational agents currently in development by three major pharmaceutical companies have already been selected for testing as part of the first phase of the trial, and will be donated by the companies with each agent representing a different drug class or type of chemical mechanism for attacking cancer.

I-SPY 2 has benefited from the unprecedented involvement of dozens of breast cancer advocates in helping to design the trial. The advocates—many of them former patients—have helped create brochures, a website, and DVD to inform patients about the trial. They have worked to ensure that the design of the trial is as convenient for patients as possible.

All results from the trial will be published by the investigators via articles in peer-reviewed scientific journals. The large amount of valuable data expected to be generated by the project will be stored in a database at UCSF and M.D. Anderson using tools developed as part of the NCI’s Cancer Bioinformatics Grid (caBIG) initiative. In order to maximize public health benefit, the not-for-profit Foundation for the NIH will serve as a trusted third party to manage data and intellectual property arising from the trial.

Trial Centers

Up to 20 of the nation’s leading cancer centers, including many of NCI’s Comprehensive Cancer Centers, will recruit and treat patients as part of the trial.  Currently selected centers include:

Technologies from Agendia (Huntington Beach, CA) and Sentinelle Medical, Inc. (Toronto, CN) will be used to measure biomarkers in the trial.

The Food and Drug Administration (FDA) has drafted a regulatory guidance describing a new  way of conducting breast cancer drug trials that promises to reduce substantially the time and cost of getting new treatments to patients. The approach is based on a trial design being tested in the I-SPY 2 TRIAL. See for a New England Journal of Medicine commentary on the Draft Guidance.

For more information:

Clinical Pharmacology & Therapeutics 86, 97–100 (1 July 2009);
I-SPY 2: An Adaptive Breast Cancer Trial Design in the Setting of Neoadjuvant Chemotherapy;  AD Barker , CC Sigman , GJ Kelloff , NM Hylton , DA Berry & LJ Esserman;

Lead Sponsor

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Alexandria logo Amgen logo Avon Foundation
Eisai logo Johnson and Johnson logo Eli Lilly logo
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