Because of an unrelated condition for which Jess Blake had been treated 18 months earlier, she would be excluded from the trial.
“We knew that that was the last hope,” Kathleen Blake recalled last week. “That was it for Jessica. … I got here to Duluth, and Jessica was already feeling bad, and then I tell her this, and … I crawled in bed with her and just hugged her for 45 minutes.”
That was on Dec. 4. Jess Blake died on Feb. 22 at age 42. Since being diagnosed with the form of brain cancer known as glioblastoma in September 2014, she had sought enrollment in a number of clinical trials, her mother said, and was turned down every time.
It left her parents, Rick and Kathleen Blake, wondering if clinical trials are too restrictive, if they keep out patients who could potentially benefit from cutting-edge treatment.
It’s a question that has been up for debate among medical experts as well.
The Food and Drug Administration, in cooperation with Duke University, is convening a public meeting on April 16 to discuss “eligibility criteria in clinical trials and their potential impact on patient access to investigational drugs,” according to an FDA notice.
If clinical trials are overly restrictive, they might not draw enough patients to give their conclusions any statistical value, said Alison Bateman-House, a medical ethicist at New York University. If that happens, the findings likely won’t be published.
“Ethically, I think that’s a huge problem because if someone lets you use them as a research subject, it’s for the purpose of having that data go out to help other people,” Bateman-House said in an interview over the phone. “So if the data just are in someone’s file cabinet and never get used, I think that’s a huge problem.”
Moreover, if the criteria for a trial are too narrow, the results may be practically meaningless, said Dr. Peter Kebbekus, the Essentia Health oncologist who treated Jess Blake.
He cited one study of pancreatic cancer patients in which the only patients who qualified were relatively young and healthy. “The average age was 56,” he said. “How is that going to help my 72-year-old?”
‘Teases, teases, teases’
Dr. Bret Friday, director of oncology research for Essentia, said some clinical trials have been overly restrictive in even the recent past, but that that’s changing.
“Most of our newer studies, those (restrictions) aren’t as much of an issue,” he said.
That’s not to say all patients are appropriate for every study, Kebbekus added.
“(There) are good reasons to exclude people,” he said. “You don’t want to be trying something new on somebody who is hospitalized and on death’s door. Because that doesn’t give you the information that you’re trying to collect.”
But for patients and their loved ones, the process of seeking to join a clinical trial and being turned down — sometimes on multiple occasions — can be heartbreaking.
Like Jess Blake, Linnea Stephan was a Duluth woman who died of glioblastoma — in her case on Jan. 3, at age 49.
“She looked and looked and looked and could never find a trial that she qualified for,” said Pat Mullen, an Allete executive who was her fiance.
At one time, she found she potentially qualified for a trial being offered at the Mayo Clinic but that she must meet with a Mayo oncologist first, Mullen related. By the time that happened, the trial was full. Only then did she learn that she could have been put on the list for the trial even before she saw the doctor.
Toward the end of her life, she was pointed to two potential trials that had “tons of promise,” Mullen said, but qualified for neither.
“It’s terrible, because it just teases, teases, teases people,” he said.
Jimmy Carter’s drug
From the time Jess Blake was diagnosed, she and her parents looked into every possible clinical trial, Kathleen Blake said. For one reason or another, she didn’t qualify for any of them.
The last was a trial Kebbekus recommended. It involves injecting the tumor with a virus to stimulate the body’s immune system, and combining that with an immunotherapy drug. In this case, the drug was pembrolizumab, the drug used to successfully treat former President Jimmy Carter from brain cancer that had spread from the skin cancer melanoma.
Such immunotherapy drugs have been a game changer in cancer treatment over the past decade, Kebbekus said.
“All of the old numbers about how long we expect people to live with metastatic lung cancer or kidney cancer or bladder cancer — we just throw it all out the window because if you respond to those immunotherapy drugs, sometimes these responses can just keep going and going and going,” he said.
Nonetheless, it’s impossible to know what, if any, difference the trial would have made for Jess Blake. A similar trial using a different immunotherapy drug for glioblastoma had been “a bit of a dud,” Kebbekus said.
“Did I have high expectations that getting on this clinical trial was going to allow her to live for years?” he asked. “I honestly didn’t. But I also knew that doing nothing wasn’t going to move her forward at all.”
Although Essentia currently is a site for between 60 and 80 oncology clinical trials, the one Kebbekus suggested for Blake isn’t one of those. So the Blakes examined the possibilities. They chose the prestigious Cleveland Clinic because of a nearby American Cancer Society Hope Lodge where they could stay.
But Blake was excluded from the trial because, 18 months earlier, she had two melanomas excised.
It was a decision that frustrated Kebbekus, and probably disappointed the people at the Cleveland Clinic as well, he said. But the trial’s authors specified the patient could have had no experience with any sort of cancer.
“What kicked her off of that clinical trial was a history of some superficial melanomas, which were never going to be the thing to shorten her life by a single day,” Kebbekus said.
Most studies now are being designed to allow for a patient who has or has had a second cancer, presuming it was treated or is under control, Friday said. In fact, Essentia Health is participating in a nationwide glioblastoma trial now from which Blake wouldn’t have been excluded because of the melanomas, he said. But it’s a “front-line” study, for people in the early stages of treatment, and it wasn’t available when Blake was diagnosed.
One hope Jess had for the treatment, even if it didn’t cure her, was that she would get her voice back, Kathleen said. She had reached the point where she often could speak only in half-sentences.
Later, when Jess could no longer speak at all, they learned that a man from the region who also has glioblastoma also had been excluded from the same clinical trial.
“She wasn’t able to talk anymore, but … she was just really upset and sad as we were,” Kathleen said of her daughter. “Here’s another person that’s being denied this opportunity for a cure and at least for hope when you have no hope.
“Obviously, it’s too late for Jessica. … But I just think it’s … essential for other people to be able to have this opportunity.”