NEW WAY OF DESIGNING CLINICAL TRIALS

March 25, 2010 — A unique collaboration is behind a "groundbreaking" clinical trial in breast cancer that is being launched in the United States. It has pulled together numerous cancer research centers and pharmaceutical companies — which would ordinarily be competing with one another — and has even involved the US Food and Drug Administration (FDA). The aim is to speed up the development of promising treatments by using biomarkers and pooling data.

The trial will test up to 12 investigational drugs, each from a different therapeutic class. The results will be shared by all the participants, and will be "broadly available to the entire cancer research and development community," according to the organizers of the Biomarkers Consortium, which is led by the Foundation for the National Institute of Health. Details of the trial were announced last week at a press briefing.

"This is an important and innovative effort in many ways," said Medscape Oncology blogger Kathy Miller MD, associate professor of medicine at the Indiana University School of Medicine in Indianapolis. "Many groups have combined clinical and biomarkers studies, but few on such a comprehensive scale."

"The public/private partnership developed to support this trial and the Bayesian statistical design, allowing investigators to adjust the number of patients needed as the information unfolds, are models that could be applied to other areas," Dr. Miller added.

Speeding Up Development

The trial, known as I-SPY 2 (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2), aims to speed up the phase 2 clinical-trial stage of drug development.

Biomarkers will be used to identify agents that are effective in specific subpopulations of breast cancer patients, said Anna Barker, PhD, deputy director of the National Cancer Institute and cochair of the Biomarkers Consortium cancer steering committee.

"This will allow us to finally design advanced, smaller, and less expensive phase 3 trials that test the right drug in the right patients," she said.

"Developing individualized medicines needs a solution bigger than one group can generate," said Janet Woodcock MD, director of the Center for Drug Evaluation and Research at the FDA. She described the Biomarkers Consortium as a "model for the future," and added that "the FDA is proud to be a founding member."

Initial Phase Will Test 5 Drugs

The initial phase of the trial will use biomarkers, such as estrogen-receptor and HER2 status, and genetic information collected with MammaPrint, and will test 5 new drugs:

• ABT-888 (veliparib), a PARP inhibitor under development by Abbott
• AMG 655 (conatumumab), an APO/TRAIL inhibitor (Amgen)
• AMG 386, an angiogenesis inhibitor (Amgen)
• CP-751871 (figitumumab), an IGRF inhibitor (Pfizer)
• HKI-272 (neratinib), a pan-ErbB inhibitor (Pfizer)

These drugs will be tested in the neoadjuvant setting in women with high-risk, fast-growing breast cancer, to see if the drug can reduce the size of the tumor before surgery. An outline of the trial design was published last year (Clin Pharmacol Ther. 2009;86:97-100).

All patients will receive the current standard of care (paclitaxel, doxorubicin, and cyclophosphamide), and most will also receive one of the investigational drugs, the Biomarkers Consortium explained in its announcement.

"The collaborative power behind this trial is truly transformational for breast cancer patients and for cancer research as a whole," said Laura Esserman MD, MBA, from the University of California, San Francisco, who is one of the principal investigators of the I-SPY 2 trial. The other is Donald Berry, PhD, from the University of Texas M.D. Anderson Center, in Houston.

"We have set up a system where everyone can learn faster," Dr. Esserman explained. The trial design allows new drugs or drug combinations to be given to more patients as soon as they prove beneficial, and allows drugs that have proven to be ineffective to be dropped just as quickly, which increases the safety of the study, she explained.

"Together, we can dramatically reduce the amount of time and the cost to bring drugs to market that can make a difference to whether women live or die," Dr. Esserman said.

The trial is expected to cost approximately $26 million over 5 years, and funding will come from a number of sources, including the food and drug retailer Safeway, Johnson & Johnson, Genentech, and Lilly.