Boot Camp For a Young Clinical Researcher

Posted in GUMC Stories

Brandon Smaglo, M.D., wants to test a combination of two cancer drugs that he suspects—and hopes—will keep different kinds of tumors at bay. But he expected it would take him a year to figure out how to translate his idea into an actual clinical protocol that could enroll participants.

The difficulty of preparing such experiments is a major impediment to many young investigators, like Smaglo, who is in his third year of a fellowship in hematology/oncology at MedStar Georgetown University Hospital. Not only must they engage busy senior researchers they happen to know for guidance, these fledgling researchers would have to convene a wide variety of experts — oncologists, molecular biologists, statisticians, pharmacologists, and on and on. The intricacies of preparing a safe, efficient, worthy clinical trial can be mind numbing, Smaglo says.

But — thanks to a unique boot camp—Smaglo accomplished a year’s worth of work in a mere week.

Smaglo won a competition for a coveted slot in a week-long workshop, held once a year in Colorado, geared to help new and promising clinical researchers quickly master this process. He joined 99 other junior investigators in July who were accepted into the AACR/ASCO Workshop on Methods in Clinical Cancer Research. The conference, organized by the American Association for Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO), is funded by the National Cancer Institute.

On hand were 60 senior researchers whose sole role was to sit down and help the researchers write their protocols.

Call it the Olympics of protocol writing — a mad dash that compresses a year’s worth of running around into a glorious sprint.

Smaglo was part of small group of eight investigators, paired with four experts in their field.

Lessons Learned for a Lifetime

“To be able to sit down with these seasoned researchers and physicians was amazing,” says Smaglo. “What seemed so complicated to me weeks ago — a process I was sure would take many months to learn and do — is much more tangible now. I basically had no idea how to run a clinical trial before I attended the workshop. Now I know what kinds of side experiments I need to do — what sort of useful data I need to collect.”

Of having the protocol in hand, Smaglo says: “There was nothing like it.”

Like many oncology researchers, Smaglo understands that “while every cancer is different, similar strategies aimed at targeting common pathways can be used across multiple tumor types.” He got the idea for his phase I clinical trial from his two mentors — Louis M. Weiner, M.D., director of Georgetown Lombardi Comprehensive Cancer Center, and John Deeken, M.D., director of the head and neck medical oncology clinic, and an attending physician at Georgetown Lombardi. Weiner was a member of the AACR/ASCSO workshop faculty for nearly 10 years, and was one of three course co-directors from 2007 to 2009.

Acting on Lab Observations

Weiner, a leader in developing new therapeutic approaches to treating colon and other gastrointestinal cancers, worked with researchers at Georgetown Lombardi and at Fox Chase Cancer Center in Philadelphia to identify a network of proteins that promotes resistance to therapies that target the epidermal growth factor receptor (EGFR).

Located on the outside of the cell, activation of this receptor “turns on” a signaling pathway within the cell that directs it to grow and divide. Some cancers are associated with the over expression or increased activity of EGFR, and thus can be treated with agents that target and inhibit this receptor, essentially turning that signaling pathway “off”.

One such agent is cetuximab (Erbitux), a monoclonal antibody used in the treatment of certain advanced lung, colon, head and neck cancers. But for most patients, cetuximab eventually stops working. Weiner found that a protein called ABL1 is likely one of the proteins responsible for cancers developing resistance to cetuximab. The discovery was published in Science Signaling in 2010.

The good news is that an approved drug exists that targets ABL1 – the drug is called nilotinib (Tasigna).

Given Weiner’s finding, Smaglo worked with Deeken to test a combination of cetuximab and nilotinib in pre-clinical studies and found that the combination of both drugs were synergistic in killing cancer cells.

Now the task is to investigate the combination of these drugs in patients whose tumors are driven by EGFR including colon, lung, head and neck cancers.

Deeken expects that Smaglo’s protocol could be approved within months followed by a phase I clinical trial under the auspices of Georgetown Lombardi’s developmental therapeutics clinic, which studies the effect of new drugs or drug combinations such as these.

“You don’t have to go to this kind of workshop to be a successful researcher, but it helps tremendously, especially in today’s research environment,” says Deeken.

Weiner agrees and explains the challenge. “We are in an era of unprecedented opportunities to make huge differences through cancer clinical trials. Paradoxically, these opportunities are challenged by equally unprecedented financial challenges for young clinical investigators, who struggle with massive educational debts, declining federal support for research and intense pressure for high volume clinical performance by academic health systems,” he says.

“The AACR/ASCO workshop is the single best course in the world for aspiring clinical investigators,” Weiner says. “It gives them the tools they need to succeed in this harrowing environment — and the lessons last a lifetime.”

By Renee Twombly, GUMC Communications
(Published August 15, 2012)