Giving Metastatic GI Patients More Treatment Options Through Big Ten Clinical Trials
Sure, a certain team from the Chicago suburbs may have beaten the Badgers on the football field last month. But while Badger fans may be a little sore about the game, UW Carbone Cancer Center oncologists are still happy to work with their colleagues at Northwestern – and other schools across the Big Ten Conference – to bring better therapy options to patients.
The Big Ten Cancer Research Consortium (Big Ten CRC), established in 2013, seeks to improve patient outcomes by providing a formal framework for oncologists from the Big Ten universities to collaborate in clinical research endeavors across institutions. This has been tremendously helpful to UW Carbone Cancer Center researcher Nataliya Uboha, MD, PhD, a gastrointestinal (GI) oncologist whose primary research focus is in the development of clinical trials for the treatment of cancers of the esophagus, the gastroesophageal junction, and the stomach.
“Participating in the consortium allows me to open trials in multiple institutions at the same time, and it’s helpful because not only can we reach out to more patients, but we can also collect data much faster,” Uboha says.
Gastric and gastroesophageal adenocarcinoma have a poor prognosis for their patients. Most patients are diagnosed at an advanced stage, once their disease has already spread beyond the primary site to other parts of the body. At this stage, the disease is largely incurable. Uboha and her colleagues in the GI clinical working group of the Big Ten CRC are developing clinical trials with combination therapies that might provide better treatment outcomes for their patients.
Chemotherapy is the standard first-line therapy, and currently, Uboha, along with her colleagues at Northwestern University, is involved in a phase II trial, BTCRC-GI15-015 , for the treatment of advanced gastric and gastroesophageal adenocarcinoma. This clinical trial, which is actively recruiting participants, investigates a new chemotherapy combination – oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX) with nab-paclitaxel – in patients with this disease.
The benefit of using multiple chemotherapeutic agents in treatment is that each drug kills rapidly dividing cells, including cancerous cells, in a different way. For example, 5-flurouracil inhibits DNA synthesis while nab-paclitaxel interferes with cell division.
Uboha is also developing another phase II trial through Big Ten CRC that treats advanced gastroesophageal adenocarcinoma patients with the combination of the immunotherapeutic agent, pembrolizumab, and another drug to boost its activity, abemaciclib.
Pembrolizumab belongs to a class of commonly immunotherapeutic agents called immune checkpoint inhibitors. Immune checkpoints are proteins on the surface of cells that signal to the immune system that they are healthy, non-foreign cells. Oftentimes, cancer cells co-opt this signaling system to evade detection by the immune system, so immune checkpoint inhibitors serve to block this mechanism. Pembrolizumab has now been FDA approved for the treatment of gastroesophageal cancers, but most patients do not respond to this treatment.
Uboha is interested in figuring out how to augment pembrolizumab activity against this disease. One promising strategy combines immune checkpoint inhibitors with a class of drugs called CDK4/6 inhibitors, which inhibit proteins that regulate cell division and growth – two hallmarks of cancers. New preclinical research in animal models suggests that this combination increases the ability of the immune system to identify tumors.
“Understanding molecular underpinnings of the disease state is essential to being able to offer the right treatment and develop new therapies,” Uboha says.
The Big Ten CRC provides a collaborative environment for oncologists like Uboha to design more clinical trials that will reach more patients and that will take advantage of the vast amounts of preclinical research conducted at institutions across the country.
Date Published: 11/13/2018