A leading-edge breast cancer clinical trial starting in September at the University of Minnesota is designed to test new targeted therapies—and it has researchers and patients alike excited about the possibilities.
Researchers at the Masonic Cancer Center are especially excited by the study’s potential to improve outcomes for women with early-stage breast cancer in a short timeframe. Called I-SPY2, the trial will compare the effectiveness of several potential new breast cancer medications in a single clinical trial and almost immediately evaluate whether they’re working.
A typical clinical trial examines one drug at a time and often involves five years of enrolling subjects and collecting data—and then another five years to analyze the treatment’s effectiveness, says Masonic Cancer Center oncologist Tufia Haddad, M.D.
But this trial is designed to move much faster.
“The testing is going to be done right up front, in real time, in women with advanced but potentially curable breast cancer,” says Haddad, who directs the University’s part of the 17-site clinical trial. “We’ll be able to monitor the tumor response to treatment and determine drug effectiveness within six months.”
The study also involves genetic analyses of breast tumor tissue, which will help physician-researchers determine which drug is most beneficial for each patient.
“Ultimately, the goal is to identify targets from the tissue—whether it’s genes, proteins, or patterns in the tumor—that predict whether or not this drug will work in this particular tumor for this particular woman,” Haddad says.
Eventually, she says, the idea is that doctors will be able to tell breast cancer patients up front which drug is most likely to give them the best results.
Different people, different treatments
This tailoring of treatments, often referred to as “personalized” medicine, grew out of the observation that patients with the same type of tumor responded differently to one standard treatment. Cancer researchers are discovering that each tumor is genetically different, even within the same type of cancer, suggesting that treatments should also differ.
“One person’s pancreatic tumor may be very different than another person’s pancreatic tumor,” says the Masonic Cancer Center’s Brian Van Ness, Ph.D. “Some people’s tumors are very aggressive, and some people’s tumors are not. Some people’s tumors respond to therapy, and some people’s tumors do not.”
But why? Likely, there are genetic variations in the tumor that will affect the way it behaves and responds to treatments, says Van Ness, head of the Institute of Human Genetics’s Division of Medical Genomics. Environmental factors also play a role, he says.
That means that different types of breast tumors, for example, will need different cocktails of drugs to treat them, says David Largaespada, Ph.D., who leads the Masonic Cancer Center’s Genetic Mechanisms of Cancer Research Program.
“It’s just something that we’ve had to face—the complexity of cancer,” he says. “That complexity doesn’t mean we should give up— it just means that this is why it has taken a long time and why it’s hard.”
But Largaespada says researchers are seeing signs of progress as new therapies show dramatic successes in subgroups of patients. Now they just need to find out why so they can help target the treatments to patients who will benefit most.
Partnering for progress
That’s exactly what the I-SPY2 breast cancer study aims to accomplish.
Women who participate in the study will receive the current standard of care, chemotherapy and surgery—widely considered the best breast cancer treatment regimen available, Haddad says—and could be randomly selected to receive one of four investigational drugs on top of that.
Breast tumor tissue samples taken before and after treatment will be analyzed as scientists look for patterns in groups of women who had the most positive results. Once these patterns are determined and new drugs are matched with these positive outcomes, the next woman who joins the trial and has that specific genetic pattern will be assigned that specific drug. This “adaptive” design is new to breast cancer clinical trials.
Masonic Cancer Center director Douglas Yee, M.D., leads the national committee in charge of selecting drugs for the trial.
Effective drugs that add to standard chemotherapy will “graduate” for testing in larger clinical trials. Drugs that do not help to improve outcomes will be dropped.
Initially, four drugs will be evaluated in the I-SPY2 study, but Yee says there are many promising new drugs on deck to take their place as others “graduate” or are dropped.
The collaborative network is a great example of how working together can help bring new treatments to patients in need faster, Yee says.
“No single institution has all the areas of expertise necessary to complete this type of clinical trial,” he says. “Everybody is very committed to making this thing happen.We all hope that this trial will be faster, smarter, and better in bringing new discoveries to breast cancer treatment.”