Advances in biology and the Web are radically altering cancer trials

For the eight years since her diagnosis in 2006, drugs, surgery, and chemotherapy had kept Debra Hinkle's breast cancer at bay.

But now, the conventional treatments were failing, and the disease was spreading. So when her oncologist decided it was time for the Bucks County woman to consider relatively untested therapies, she was more than willing.

"I thought that if I didn't do a clinical trial now, maybe I wouldn't be able to later," said Hinkle, 54, who lives in Newtown Township and works as a software-development project manager.

So four months ago, she enrolled in a trial study at the University of Pennsylvania's Abramson Cancer Center that combines a decades-old chemotherapy drug with a newly developed medication in hopes that the combination will be more powerful against metastatic breast cancer than either would be alone.

And while it's much too early to say how effective the new treatment will be, Hinkle is happy to be part of a new world of clinical trials, a wave of scientific discovery that she hopes can stay ahead of a disease that remains incurable, although patients' lives may be prolonged for years.

In recent years, advances in biology and the Internet have radically changed cancer trials in the United States.

Patients are finding out about studies of new medications online, sometimes virtually shopping for trials even before they ask their physician about them.

And the trials themselves are changing, in many cases becoming smaller and nimbler as physicians find they need fewer patients to discover what works and what doesn't, sometimes adjusting dosages as they go along.

Hinkle's trial at Penn, which combines the chemotherapy agent paclitaxel with the newer drug palbociclib, has just 21 patients enrolled.

"We're slicing and dicing the disease into smaller and smaller pieces," says Donald Berry, a professor of biostatistics at the M.D. Anderson Cancer Center in Houston and an expert on trial design. "'Personalized medicine is coming to the forefront, treating individual patients or small categories of patients," sometimes targeting a patient's tumor based on its genetic makeup: "Biology is sort of driving the bus."

Large and lengthy blockbuster trials are becoming less common, Berry says, as researchers get better at figuring out which patients are more likely to benefit from the therapy.

Bigger trials are being broken into smaller subsets, says Anthony J. Olszanski, director of early clinical development at Fox Chase Cancer Center. And researchers are getting better at seeing early in the trial what is working and what isn't, Olszanski says.

Still, the expansion of all kinds of medical research, including cancer trials, is threatened by reductions in federal funding.

"The golden age of making advances against cancer was when the federal government was supporting a very vibrant, cooperative group system, where the investigators in the United States banded together to answer the critically important questions," says Larry Norton, medical director of the Evelyn H. Lauder Breast Center at Memorial Sloan Kettering Cancer Center in New York.

"That's been severely curtailed by dramatic cutbacks in federal support. We're just trying to keep the engine going, and we're starved for gasoline."

"It used to be that clinical trials were looked at as sort of a last-ditch effort," says Amy Clark, Hinkle's oncologist at Penn. "Now, people are reaching to clinical trials much earlier because they recognize that some of the drugs we're studying have less toxicity and may be more efficacious."

In Hinkle's case, the relatively low dose of chemotherapy she receives every Thursday, combined with a long-approved drug that has few side effects, allows her to be back at a very demanding job by Monday: "It hasn't affected anything I do from a work perspective."

About 1.6 million new cases of all types of cancer, and more than 575,000 deaths, are projected in the U.S. this year, says Vikas Sukhatme, a professor at Harvard Medical School, but only 5 percent of adult patients are in clinical trials. (The figure is higher for pediatric cancer.)

Many cancer patients are ineligible because they have other complicating medical conditions that would make it difficult to isolate the effect of the drug being tested. But 5 percent is still too low, Sukhatme says.

"We need to encourage patients to enroll from day one," he says.

In many cases, they enroll because of what they learn online. In 2007, the Food and Drug Administration vastly increased the amount of detail that must be posted for all clinical trials on the federal website ClinicalTrials.gov.

"Patients have information they've never had before," says Robert Vonderheide, an oncologist at Penn's Abramson center, who has designed a study combining a new drug he synthesized with an older drug traditionally used for immunosuppression in organ transplants. "Patients and their physicians now have this incredible ability to go online and find studies."

"It's an Internet-savvy group," says Martha Sweeney, a clinical-research nurse at the center. "I'm amazed at what some of these patients find. Some of them actually hire scientists to review studies for them and recommend which trials to go on."

Sweeney recalled a pancreatic cancer patient who drove from Arizona in her camper and stayed in Chester County for the first, most intensive, month of the trial. Then, for two additional months, she flew back and forth on a friend's frequent-flier miles.

Despite medical inflation, the research budget for the National Cancer Institute, the largest single funder of cancer trials, has been virtually flat since 2003, when it was about $4.8 billion. In 2012, it was about $5 billion, not adjusted for inflation.

Sen. Robert P. Casey Jr. (D., Pa.) was so alarmed that he cosponsored a bill with Sen. Dick Durbin (D., Ill.) that would create a separate trust fund for biomedical research, similar to the highway trust fund.

The research fund would be exempt from any sequestrations, the deep, automatic funding cuts that resulted from Congress' failure to agree to more carefully thought-out budget reductions, which Casey calls "a really dumb idea. "

Robert Comis - an oncologist who heads the Philadelphia-based Coalition of Cancer Cooperative Groups, organizations that run clinical trials - estimates that the federal government was supporting trials for up to 27,000 cancer patients in 2006. That is now down to about 21,000, he says, and, with further cuts proposed recently, could go well below that.

Since physicians can't ethically drop patients from ongoing trials, the cuts will be reflected in trials that don't get started. "What suffers are the new things," Comis says. "It's not driven by [research] opportunity; it's driven by budget."

While the pharmaceutical industry is still a major player in cancer trials, he says, it tends to remain focused on testing new drugs rather than therapies that rely on different uses or combinations of older drugs.

"There are a lot of issues the pharmaceutical industry isn't interested in," Comis says. "There has to be give and take between the public side and the private side."

The study in which Hinkle is enrolled, for example, is financed by both the Abramson center and Pfizer, which designed palbociclib and is providing the drug to enrolled patients.

In contrast, the study that Vonderheide designed, involving an old drug and a new one that does not yet have a major manufacturer, is supported by the Breast Cancer Research Foundation.

New discoveries about cancer call for more and more kinds of treatments. "Breast cancer is now considered to be at least six, maybe 10 diseases," Comis says. "It's a conundrum for industry to determine exactly how they're going to handle this."

In the palbociclib study at Abramson, Penn researchers are calling the shots. "It lets us think outside the box," says the lead investigator, Angela DeMichele. "It lets us be a little more nimble and creative in our approach."

There is no end point to the study. Hinkle and other patients will be able to stay in as long as the drug combination seems to be working. If they find chemotherapy too taxing, even at a lower dosage, they can go on palbociclib alone.

"It gives me a sense of hope and peace about the disease," says Hinkle. "A minute I think about dying is a minute I'm not having fun."