A phase for life
By Lynne Anderson, Photography by Jack Kearse
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1. Carolyn Higgins, who has multiple myeloma, is one of 200 patients who are helping Winship Cancer Institute doctors and nurses evaluate new cancer drugs for the first time in humans.
Carolyn Higgins is cheery-eyed with a bright smile, a package of cheese and crackers in her hands. Nearby are two small chocolates still in wrappers. She looks as happy and relaxed as if she's lying on a chaise on a sunny beach.
"I'm sorry," she says sheepishly, referring to the food. "I forgot my lunch."
But on an adjacent chair, zipped plastic bags hold her belongings. An IV is inserted in her right arm, slowly delivering an experimental drug that she has been getting for three years into her vein.
That she has advanced multiple myeloma seems to bother Higgins not at all. She also seems unconcerned that the standard, FDA-approved drugs used to treat myeloma failed to work for her. Higgins is thrilled to be alive three years into a phase 1 clinical trial that tests the safety of a drug developed at the Winship Cancer Institute for multiple myeloma.
"I'm starting my fourth year," she says, sounding like a kid who's tricked her mother into letting her stay up way past bedtime. "This drug and I are best friends."
Higgins is one of almost 200 patients who participated in phase I clinical trials at Winship last year. Opened in 2009, the phase 1 unit is at the heart of the institute's drug development program. It is one of only two such units in Georgia and by far the largest and busiest, with 38 trials in 2011. Already, phase 1 research at Winship has led to four drugs in the FDA approval pipeline as well as another 24 drugs still under study. Among them, a drug developed by Higgins's oncologist, Sagar Lonial, is coming up for FDA review within a few months.
Just this year, two trials led by Suresh Ramalingam have moved into larger, multi-center phase 2 investigations that will test the efficacy of new agents to treat lung cancer. Both trials tested a combination of drugs, the first a combo of docetaxol and a newer agent known as STA9090. The second combined a PARP inhibitor (a drug that knocks out a cancer cell's repair mechanism) with chemotherapy.
And according to the New England Journal of Medicine, another Winship trial has shown promise against some solid tumors that have been difficult to treat in the past. Led by John Kauh, the study evaluates an antibody that blocks the protein PD-1. Earlier Emory Vaccine Director Rafi Ahmed had discovered that PD-1 acts as a brake on immune cells. In the current study, the antibody has allowed tumors to regress and stabilize in patients with advanced cancer (including non-small cell lung cancer, melanoma, and renal cell cancer).
The phase 1 unit, tucked into a quiet but busy corner of Winship, occupies only 2,100 square feet, roughly the size of a family home. For many, it will become another sort of home—a place where a shared sense of purpose connects a disparate group of people and unites them against a common enemy, in this case, cancer.
These people also share common beliefs—not only does scientific research pay off but also life is made more meaningful by doing something for others.
Phase 1 trials are those in which drugs that have shown promise in laboratory studies are first administered to humans, alone or in combination with other drugs. Usually such a trial involves between 20 and 100 patients. Some of the drugs that are tested will go on to gain FDA approval, curing people of cancer or extending their lives for many years. The main purpose, however, of a phase 1 trial is to determine whether a drug is safe for use in humans, and if so, at what dose and over what time.
Although most of the patients in the phase I unit have an aggressive cancer that has failed to respond to standard treatments, hope remains palpable. Each patient brings to the unit his or her own private reasons for taking the bold step of letting doctors and nurses try a first-in-human treatment. Some speak of their grandchildren, wanting to live to see them graduate. Others talk about a brother or sister in whose memory they fight. All face possible unknown side effects, and many spend long days in the unit, dozing, watching TV, laughing with nurses—and always hoping.
"When we give a new drug, we want to know, did it get to the cancer cell? Did it get to the proteins we wanted? And how long did it stay in the body?" says R. Donald Harvey, director of the phase 1 unit. But patient safety remains the priority.
Rigorous standards apply to these trials, and oversight—both internal and external—is appropriately intense. Higgins says that she has been so closely monitored that she thinks of the unit as a VIP suite. "They don't just attend to you, they hover," she says.
Nurses, doctors, and director alike all listen to patients attentively. Nurses draw blood or check temperatures and other vital signs as often as every 20 minutes. Patients arrive as much as two hours early for their lab work, and they typically wait at least two hours after they receive the drug, usually administered intravenously, before they are allowed to go home. For some, the treatment adds up to a 12-hour day.
The patients who enter clinical trials are pioneers, not only possibly extending their own lives but also helping unravel the mysteries of some of the most persistent diseases.
"It's a testament to the patients we have," says Harvey. "I'm lucky to be able to serve them, to get to know them, and to offer something they wouldn't be able to have otherwise."
Patients as teachers
Clinical trials today are the basis of nearly all new drugs and medical devices that gain FDA approval and come to market. Basic scientists often labor for years trying to find a new pathway, a new protein, or a new molecule to target to treat a disease. When an agent has proved promising in animals, investigators then evaluate it in humans.
With cancer, the drug discovery process is particularly challenging. Scientists now know about the vast complexities of cancer, the many subtypes within a broader field of cancer, and how cancer cells can and do mutate to avoid cell death.
"In most patients with cancer, there are many molecular drivers," says Harvey. "We don't have just a single protein or a single pathway. The challenge is in finding out in any given patient what the molecular drivers are—and that's just the first step. The next step is finding drugs that effectively inhibit those targets and are well tolerated." And Harvey adds, "that's with the understanding that resistance to these targets may arise."
Winship's phase 1 unit goes a long way toward gaining knowledge about whether certain therapeutic agents will be well tolerated. While researchers and clinicians are careful in using the word "cure," they all hope that the drugs being studied in phase 1 will lead to advances.
"We're looking for successful signals that will translate to a broader community of patients and clinicians," says Harvey.
Patients who decide to participate are brave, he notes, and the staff in the phase 1 unit do everything they can to support these pioneers.
"We all get excited when they get good scans, and we're there for them when they don't get good ones," says Emory nurse Claudia Giddings, one of four full-time nurses in the unit. "We're together. We're a team. We're here to celebrate more birthdays."
Patient Martha Byrd of Canton, Ga., says that she chose to participate in a phase 1 trial to do just that—to celebrate more birthdays, not only her own but her grandchildren's too. Originally diagnosed with breast cancer, Byrd learned in further scans that she also had unrelated pancreatic cancer. The breast tumor responded to chemotherapy, but the cancer in her pancreas did not.
Byrd pondered enrolling in the phase 1 study for some time. "I am the type of person who will get a prescription and read the side effects and say ‘no,'" she says. There was another big concern—her job. Byrd needs to work 30 hours a week to maintain her insurance, and she worried about the side effects. Determined, she has worked out a way to keep her job and still receive treatment, with her boss allowing her to work from home on Wednesdays when side effects tend to be hardest for her to handle.
The thought of living to see her grandchildren graduate from high school inspired her, she says. "I've always had a lot of faith in my doctors," she says. "The people here are just incredible. They answer all our questions, and they take such good care of us."
The physicians and nurses conducting the phase 1 trials wouldn't consider doing anything less. They view their patients as heroic and take their own roles very seriously. "It's a tremendous responsibility," says Ramalingam, and Kaugh adds, "everyone here realizes that."
Giddings says that the patients inspire her to give her best every day. "They're resilient," she says. "I figure if they're that resilient, we're going to be there for them however we can."
Harvey, too, credits the patients for what they have taught him about courage and their experiences on the various drugs.
"I'm most grateful to them for the learning I've been able to do," Harvey says. "Without them, we're lost in the wilderness."