Unique Clinical Trial Design Accelerates Personalization of Breast Cancer Treatment

An innovative national clinical trial underway at Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center and Georgetown University Hospital, expedites the screening of promising new drugs for women with early stage but high risk breast cancer - women for whom an improvement over standard treatment could dramatically change the odds of survival.

The I-SPY 2 ("Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis -2") trial tests individual patients' tumors for genetic or biological markers ("biomarkers") to assess the risk of disease recurrence and screen for potential benefit from promising new treatments. In addition, an innovative trial design enables researchers to use data from one set of patients to guide decisions about which treatments might be more useful for patients later in the trial. This approach, called adaptive randomization, will help researchers learn more quickly which investigational drugs will be most beneficial for women with certain tumor characteristics and eliminate ineffective treatments more quickly.

"I-SPY 2 promises to leverage convergence of progress on a number of research fronts to speed the evaluation of promising new breast cancer drugs using molecular cancer biomarkers to identify those agents that are effective in specific subpopulations of breast cancer patients," says Anna D. Barker Ph.D., deputy director of the National Cancer Institute and co-chair of The Biomarkers Consortium Cancer Steering Committee. "This will allow us to finally design advanced, smaller and less expensive Phase III trials that test the right drugs in the right patients."

Georgetown Lombardi is one of 20 major cancer centers in the U.S. selected to participate in the I-SPY 2 trial. Sponsorship is provided by the Biomarkers Consortium, a unique public- private partnership managed by the Foundation for the National Institutes of Health that includes representatives from the U.S. Food and Drug Administration (FDA), the National Institutes of Health (NIH), and major pharmaceutical companies. Funders include the Safeway Foundation and several pharmaceutical industry partners.

"The goal of I-SPY 2 is to use an individual's tumor characteristics to identify the most effective combination of anti-cancer agents as early in the treatment course as possible," says the Lombardi lead investigator, Minetta Liu, M.D., director of translational breast cancer research. "At the same time, we will also be able to accelerate drug development and reduce the cost of testing medications."

I-SPY 2 is designed for women with newly diagnosed advanced breast cancer that has not spread. About 800 women with breast cancers characterized as high-risk and fast-growing will be enrolled in the study prior to surgery. All patients will receive the current standard of care, and most participants will receive one investigational drug to see if adding another agent will lead to more significant reductions in tumor size before surgery and ultimately to more improvements in survival. A distinctive feature of the trial is that it will screen multiple drugs from multiple companies - up to 12 different agents over the course of the trial. Testing several drugs simultaneously through this adaptive design should allow the most effective ones to reach late-stage trials more quickly.

I-SPY 2 has the potential to significantly reduce the cost of drug development and bring safe and effective new drugs to market more efficiently. According to The Biomarkers Consortium, 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 for assessments of drug activity much earlier in the research process, potentially resulting in drug development and approval with clinical trials that require a smaller population of patients, less time and far fewer resources. The goal is to shave several years and hundreds of millions of dollars off the current process.

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. The agents will be donated by the companies with each agent representing a different drug class or type of chemical mechanism for attacking cancer. The first agents expected to be tested include:
• ABT-888 (veliparib), a PARP inhibitor being developed by Abbott Laboratories, Abbott Park, IL
• AMG 655 (conatumumab), an APO/TRAIL inhibitor and AMG 386, an angiogenesis inhibitor, both under development at Amgen, Thousand Oaks, CA
• CP-751,871 (figitumumab), an IGFR inhibitor and HKI-272 (neratinib), a Pan ErbB inhibitor both under development at Pfizer, Inc., New York, NY

Click here for more information about I SPY 2 . Patients seeking more information about this study and other clinical trials at Lombardi can call 202-444-4000.

Source: Georgetown University