Patients like Joel Groebner and Ellen Smith are examples of people living at the cutting edge of medical science. Both are taking “experimental” cancer drugs, and the therapies are keeping their diseases in check.
Cancer clinical trials—the highly regulated and monitored system that tests new drugs, new combinations of drugs and other treatments that are not approved for use by the Food and Drug Administration—are part of standard care at academic cancer centers like the University of Colorado Cancer Center.
Today, nearly every patient at the center’s lead care partners—University of Colorado Hospital and Children’s Hospital Colorado—are evaluated to see if can be offered the option of a clinical trial. Evaluation often includes testing each patient’s tumor to see if the genes, proteins or other biologic factors the experimental drug targets are present. Patients are also evaluated for a host of other factors, including their general health status and the treatments they’ve been on before.
Not all cancer patients are on a phase I clinical trial. In fact, those trials are usually reserved for patients for whom standard treatments have failed. The experimental drug may be their best remaining chance for a response.
FIRST IN MAN
New therapies are tested extensively in animal models to see if they work—kill cancer in the way they are designed to—before they are brought to people. Often the drugs are created by pharmaceutical companies, and the companies come to academic cancer centers to “translate” the successful lab discoveries into human patients via a phase I clinical trial.
These so-called first in man trials aren’t looking for whether the drug kills the cancer. Instead, the goal is to determine how it behaves in a human. The clinical trialists—physicians and nurses trained to specifically conduct clinical trials—are looking for dose-limiting toxicities to characterize the body’s general tolerance of the agent. The first group of patients gets the lowest dose, and then the amount of the drug or frequency is increased until patients get intolerable side effects. When that dosage is determined, the drug can move on to phase II testing, where further efficacy testing comes into play.
Sometimes, a small percentage of patients will see their tumors shrink or disappear with an experimental agent. In the past, when trial data was collected on paper and analyzed months after all patients had completed the protocol, these patients were often overlooked. But today, data goes back to the trial sponsors within days or even hours of the patient visit thanks to electronic medical records and databases.
Real-time access to what’s happening in that patient allows doctors to notice trends when they can be taken advantage of. Time is money, and time is life for these patients.
If a small number of patients respond to the drug, clinical researchers can usually figure out what the commonalities are and open a secondary arm of the trial that enrolls only patients with those features. That’s what happened with crizotinib and patients with the ALK fusion protein in lung cancer, and as a result, the drug is now approved by the FDA for treating those patients just three years after it entered phase I trials.