Last year, Beth Shia got the worst news a breast cancer survivor can get.
Her disease was back. For a third time. Despite two sessions of chemotherapy and radiation.
“I knew it wasn’t good ... I know what metastatic breast cancer means,” Shia said later.
It was time, she thought, to put her affairs in order and focus on quality of life, rather than fighting the disease.
But Shia's doctor, Dr. Jacqueline Vuky, is an oncologist with the OHSU Knight-Legacy Health Cancer Collaborative. She enrolled Shia in their new system of clinical trials, called "Serial Measurements of Molecular and Architectural Response To Therapy" or SMMART.
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This is not just another clinical trial. When Nike co-founder Phil Knight pledged half a billion dollars to the OHSU Knight Cancer Institute, he asked researchers to throw out the old way of doing things in favor of something completely new.
Rather than trying to find the next blockbuster drug, researchers focus on trying to cure each individual patient's cancer. That's a very different approach, involving everything from profiling a tumor's DNA so it can be easily targeted to trying to kill it with a cocktail of drugs that may not yet be federally approved for cancer.
“In this day and age I think it’s very important for oncologists to be aware of all these new trials," Vuky said. "Because there exist these instances, such as Beth, who has had a complete response from the treatment at this point."
It’s true. By profiling her particular cancer and using two drugs that hadn't been used in combination before, Shia now has no detectable cancer — and that’s after her cancer had metastasized and spread to her brain and lungs.
For Shia the new approach to clinical trials led to a procedure known as precision immunotherapy. For another patient, it could lead to a completely different approach.
"This is just as good as it gets," said Dr. Gordon Mills, who heads the SMMART trial.
Dr. Gordon Mills heads OHSU Knight Cancer’s new SMMART trial. He came to Oregon to change the way clinical trials are conducted. “The idea of a patient as a guinea pig, is not where we are today,” he said.
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A few years ago, he was leading programs at the largest cancer center in the nation, MD Anderson Cancer Center at the University of Texas.
But he was frustrated. He didn’t like the fact that, in many clinical trials, new drugs were being tested on patients who didn’t necessarily benefit.
“The idea of a patient as a guinea pig is not where we are today,” he said.
Mills complained to everyone, including the top officials at OHSU.
“I came and gave a presentation on how we wanted to change the way we treated cancer," Mills said. "The people here embraced that so thoroughly, that I literally had no choice but to come."
Now Mills heads a team of 120 scientists working on the SMMART Trial.
When a new patient enrolls, they make an enormous effort to understand that patient’s individual cancer. They check the tumor’s DNA, its RNA, its protein emissions and its exact location. They analyze the patient’s individual immune system, give them CT scans, MRIs and so on.
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All those tests can cost $50,000 or more. And that's before any specific course of treatment is established.
Once researchers have profiled the tumor, said Mills, they scour medical databases across the world to see if similar cancers have been successfully treated.
If they haven’t, which is most of the time, OHSU researchers then custom design a treatment for that one patient, picking from dozens of powerful drugs.
Some of those drugs have been approved by the U.S. Food and Drug Administration, but others might be in the early stages of testing.
Mills said they generally start with one drug. But then they might add another and another — even if the drug hasn’t been FDA approved for cancer.
“Where we are combining drugs that have never been combined before, we went to the FDA to get permission," Mills said. "You know what’s safe for each drug, you know the toxicity of each drug. You can use that information to get your best idea of what a safe starting dose will be."
What they’re doing is similar to how scientists first began successfully battling HIV in the 1980s and '90s — they used a cocktail of different drugs to fight different aspects of the disease.
The other thing the SMMART trial does differently is monitor tumors as they change when exposed to drugs.
"The information we get from that change, over time, under stress with our therapy, is far more informative than looking at that single initial biopsy," Mills said.
When a new patient is enrolled in the SMMART trial, reserchers check the tumor’s DNA, its RNA, its protein emissions and its exact location. They check the patient’s individual immune system, they given them CT scans, MRIs and the list goes on — all to tackle that one patient's individual cancer.
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Mills said that means taking two and sometimes three biopsies to see what a drug is doing to a tumor. In normal clinical trials, patients are often reluctant to do a second biopsy because it won't affect their cancer, explained Dr. Zahi Mitri, an assistant professor of medicine at the OHSU Knight Cancer Institute.
“How we’ve done clinical trials before, is you do a trial for a couple of years. You get the results about four years later. And you never benefit the patients who were actually on that study,” Mitri said.
He said Knight Cancer patients are more likely to agree to biopsies because they know the results may help their particular case.
The ultimate goal is to avoid biopsies entirely by developing new, less painful tests, say ones that can provide information about a tumor from a simple blood draw.
“How we’ve done clinical trials before, is you do a trial for a couple of years. You get the results about four years later. And you never benefit the patients who were actually on that study," said Dr. Zahi Mitri.
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On top of all the biopsies, tests and new drug regimens, researchers will also use chemotherapy, hormonal therapies, immunotherapy — anything to fight that one individual’s cancer.
This new SMMART trial puts the OHSU Knight Cancer Institute at the forefront of what’s known as precision medicine, essentially treatment tailor-made for an individual.
Researchers' hope is that over time, they’ll build a database of many different types of cancers, their DNA profiles and their successful treatments that can be shared around the world.
The other big hope for researchers is that patients will eventually be able to battle their cancers at home, rather than trekking across state to OHSU all the time. Their regular doctor could send in various tissue tests, let the OHSU Knight Cancer Institute research a possible treatment, and then administer that treatment themselves, in the patient's hometown.
Back at OHSU, Beth Shia’s doctor pulled up a cross section of her lungs on a computer screen and explained there’s no evidence of cancer.
“It was beyond what I’d actually ever hoped was possible,” Shia said.
Now she plans to spend her retirement traveling with her husband and visiting their grandchildren.