Opening any clinical trial requires the satisfaction of many regulatory requirements for very good reasons. Scores of people review applications, confer in committees, weigh risks and benefits, all to make sure that the investigator has patient safety as their guide. This process is important, but it can also be lengthy and overlong delays can doom a trial before it can even begin recruiting. This is especially perilous for Phase I clinical Trials, which can face higher regulatory and coordination burdens than Phase II or III trials.
For the last year, under the direction of medical oncologist Yousef Zakharia, MD, a Phase I clinical trial working group has sought to avoid those early collapses. The new dedicated multidisciplinary team within UI’s Holden Comprehensive Cancer Center (HCCC) has been working to streamline the application process to bring more Phase I trials online and manage them through recruitment and administration. In less than a year, the HCCC has dramatically reduced the time moving trials through the regulatory process and more than quadrupled the number of active Phase I trials on offer.
“When we first started to talk about creating the group, we had about 5 to 10 Phase I trials a year here,” Zakharia said. There are now more than 40 Phase I trials in progress in the HCCC. Typically, from inception to approval, Zakharia said, the process used to take longer than 6 months; the group is striving to shave that down to a consistent 2 to 3 months.
Traditionally, the administrative tasks of launching a Phase I trial were handled by teams embedded within disease-specific groups. Each time they would move to begin a new trial, there was a period of re-learning the steps or becoming familiar with any changes since their last application. But by identifying dedicated staff to handle the work for them, experience translates to efficiency.
The dedicated team is composed of more than 20 members, Zakharia said. There are regulatory personnel, financial administrators to communicate with sponsors, dedicated nurses to monitor progress and any adverse effects, data managers, and the investigators themselves. “Our experienced investigators are eager to bring in more Phase I trials to help our patients.” The entire group meets twice a month to review the status of all trials, the accrual process, and to collaborate on how best to overcome any current obstacles. “Being at a large NCI Comprehensive Cancer Center and large academic institution offers us a distinct opportunity to move promising molecules and ideas from our basic scientist colleagues’ labs to the clinics, and vice versa,” Zakharia said. “If we have a scientific question or clinical observation, we can go back to the lab to vet it further through translational research. This is a unique opportunity and a priority for our program to help move the science forward.”
Zakharia cites the mentorship of Oncology Section Chief Dr. Mohammed Milhem for helping him develop his skills to lead the Phase I program. Milhem is quick to praise Zakharia’s enthusiasm for the team’s success. “I tend to view the division as a large pirate ship,” he said, stressing their camaraderie and willingness to embrace radical ideas. “Yousef is the sail that really drives our speed and takes off pulling the ship forward. I am happy to see him embrace his leadership position as our Phase 1 Director and, with his momentum, push us to excel as a group.”
Now that the group has found its stride, the program is ready to expand. “Our goal is to have a trial available for every patient who comes to see us.” Because University of Iowa Health Care and the HCCC is a large referral center both for the entire state and parts of many surrounding ones, the need to offer a wide variety of treatment options for refractory cancers is great. “It is a heavy lift,” Zakharia acknowledges, “but we certainly can do it, because we have all the resources and expertise to achieve it.”
When asked what motivates him in the face of such challenges, Zakharia’s face lights up. “It’s hard to describe the satisfaction level. If you are using a new drug with extensive science behind it, and you find it working for your patient, the happiness is unmatched. Being able to bring my patients innovative treatments, fresh out of the lab, to help shrinking their disease or even stabilizing it, that is the utmost happiness. That’s what keeps me coming here on a daily basis.”