Young Investigator Takes Aim at Drug Resistance with First Clinical Trial


Work that could take seasoned investigators years has been dramatically expedited for a new researcher at Georgetown Lombardi Comprehensive Cancer Center.

Brandon Smaglo, MD, a young researcher-clinician, has launched an exciting clinical trial within his first few months as a new faculty member at Georgetown University Medical Center (GUMC). The trial, which seeks to test a novel combination of two cancer drugs that he hopes will keep cancer at bay, is already enrolling its first patients.

Georgetown Lombardi Director Louis M. Weiner, MD (left), and Brandon Smaglo, MD. Weiner is among Smaglo's mentors and collaboratorsGeorgetown Lombardi Director Louis M. Weiner, MD (left), and Brandon Smaglo, MD. Weiner is among Smaglo's mentors and collaborators

Smaglo had an unusual head start. Last year, as a third-year fellow in hematology/oncology at MedStar Georgetown University Hospital, the clinical partner of GUMC, Smaglo won a competition for a coveted slot in a week-long workshop geared to help promising junior clinical researchers quickly master the process of writing and submitting protocols for clinical trials.

With direct mentoring from senior researchers, Smaglo was able to accomplish basically a year's worth of work in a mere week, and now the resulting study is moving full steam ahead.

"A big part of my last year of fellowship was taking the protocol through the review committee process. Now it has been approved – the [Food and Drug Administration] said it's a go, Georgetown has said it's a go. So we are moving forward," says Smaglo, who is part of the Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown Lombardi.

Overcoming Drug Resistance

Smaglo and his colleagues from Georgetown Lombardi will test whether a combination of two drugs that have been shown in pre-clinical studies to overcome drug resistance are tolerable and effective in cancer patients.

One of the drugs, cetuximab, is already used to treat advanced colon cancers, as well as head and neck cancer. But for many patients, cetuximab stops working after a period of tumor control.

Researchers from Lombardi, in collaboration with the Fox Chase Cancer Center, have identified a network of proteins that may be responsible for this drug resistance.  Drawing on this research, Smaglo and his colleagues think that by adding another drug in conjunction with cetuximab, they may be able to disable a key protein in this network and overcome the resistance.

The other drug, nilotinib, is already approved by the Food and Drug Administration and has been shown to be efficacious in other cancers. Smaglo's study will evaluate the combination of cetuximab and nilotinib in eligible patients to determine if it is more tolerable and more effective than cetuximab alone.

"Nilotinib is new to this disease type, but it is not a new drug. There is a lot of good experience with its use in leukemia and some data for its use in gastrointestinal stromal tumors," Smaglo says.

"We have good reason to think that the use of nilotinib with cetuximab will prevent tumors from becoming resistant to therapies."

Smaglo says he hopes the study will enroll between 19 and 22 patients over the next year.

Doing Better by Patients

The problem of drug resistance underscores how complex the cancer protein network is, Smaglo explains. The questions that need to guide cancer research are those that look at the heterogeneity of each tumor, and at how tumors are changing in response to the therapies patients receive.

"We need to look at how we can manipulate the cancer protein network to anticipate resistance to the drugs we are using – this is a step towards personalizing therapies," he says.

"We can do better by our patients not just because we have a drug that works in some patients, but because it is the right drug for the right patient."

Goodbye to 'Cookie-cutter' Approach to Training Doctors

Smaglo wears several hats at Georgetown. Besides conducting active research, Smaglo is also senior clinical instructor at the Georgetown University School of Medicine, attending physician at MedStar GUH and now the associate program director for the hematology/oncology fellowship program.

Having just completed the fellowship program, Smaglo feels he has a unique perspective to lend under the leadership of Program Director Bruce Cheson, MD.

"We are redesigning some aspects of the curriculum in response to feedback from fellows. They really like the access they get to faculty, but they also want more research time and more exposure to the clinic," Smaglo says.

Much like cancer therapies, Smaglo believes that the training of fellows cannot be a "cookie-cutter approach" – but that they should be flexible and adaptive to fellow's specific needs.

"Our plan is to make sure that fellow have the mentorship to help them decide what they want to do with their career, and to tailor a second and third year experience that will enable them to be as competitive as possible," he says.

"'One-size-fits-all' no longer applies to a doctor," Smaglo adds.

By Lauren Wolkoff, GUMC Communications
Published November 19, 2013