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Clinical Trials Game-Changer?

A new type of clinical trial aims to identify which drug is the best fit for each patient’s tumor. Can this innovative model expedite new drug approvals? Story by Sue Rochman & illustrations by Mikey Burton

When Larisa Kure was diagnosed with breast cancer in July 2011, she assumed her treatment would begin with surgery. But when she met with her doctor at the University of California, San Francisco (UCSF) Carol Franc Buck Breast Care Center, she was told that she had another option: taking part in a clinical trial in which she would have chemotherapy before her tumor was surgically removed.

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New clinical trial designs could lead to better results.

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Intrigued, Kure asked for more information. She soon learned that UCSF had recently launched a clinical trial known as I-SPY 2, and her tumor’s stage and size made her eligible to participate. Giving therapy before surgery—called neoadjuvant treatment—would allow the researchers to investigate whether the chemotherapy drugs made her tumor smaller, and if so, how quickly. But there was more: By studying Kure’s tumor tissue, the researchers hoped to identify genetic or biological markers (known as biomarkers) that could be used to predict the drugs to which a tumor like hers would respond.

Like other cancer clinical trials, I-SPY 2 was launched to identify effective new treatments. (Its title is ​ short for “Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2.”) But I-SPY 2 and its predecessor, I-SPY 1—along with a series of lung cancer trials called BATTLE (Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination)—were also created to challenge the current system for testing new treatments, which is notoriously slow. What sets them apart from other studies is that their primary goals aren’t to get specific new drugs approved. Instead, their missions are broad: to establish new models for clinical trials that help researchers quickly identify both the therapies that are most effective and the tumor biomarkers that indicate which patients will respond best to those therapies.   ​

Kure liked what she heard. And it didn’t take her long to agree to take part. “It’s terrible to have to go through this,” she says. Knowing this trial will  “at least allow us to get some knowledge that might help others down the road,” Kure says, “makes it feel a little better.” 

A New Approach to Clinical Trials
For the past five decades, researchers have tested the safety and effectiveness of new cancer drugs by promoting them step-by-step from the lab, to small phase I studies, to slightly larger phase II studies. Promising results in phase II clinical trials would encourage pharmaceutical companies to lay out the big money for large phase III trials, which are designed to show whether the new treatment is better than the current standard of care.

The process is time-consuming and expensive: It takes an estimated 10 to 15 years and costs more than $1 billion to develop a new drug and bring it to market. And the success rate is incredibly low. Only about 6.7 percent of cancer drugs in phase I clinical trials achieve approval by the U.S. Food and Drug Administration (FDA), according to the Biotechnology Industry Organization. (Drugs in phase I testing for other diseases are somewhat more likely to gain FDA approval; their success rate is around 12 percent.) What’s more, explains I-SPY principal investigator Laura Esserman, a surgical oncologist and the director of UCSF’s Breast Care Center, success has all-too-often been defined by statistically significant, but small, improvements that frequently didn’t translate into large gains in actual patient outcomes. 
It takes an estimated 10 to 15 years and costs more than $1 billion to develop a new drug and bring it to market. 

The I-SPY and BATTLE trials were designed to enhance the value of phase II trials by using them to get information that can result in phase III trials that will test drugs in the patients most likely to benefit from them—making the process faster and more efficient. And both trials shifted the focus of drug testing toward two promising areas: the evaluation of therapies that home in on specific genetic errors that make a tumor tick, and the identification of biomarkers that indicate which tumors will respond best to each drug.

“If you understand that breast cancer is a heterogeneous disease,” says Esserman, “then you can’t use the same drug on everyone. It doesn’t work.” Instead, “you need to start at the beginning with biomarkers and you need to have an efficient mechanism to test multiple agents at once and to see which drugs work” in which tumors.


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