July 8, 2019

Clinical study tests drug that may prevent cancer metastasis

A clinical study of a drug that may block cancer metastasis is currently enrolling patients at the Vanderbilt-Ingram Cancer Center.

Ingrid Mayer, MD, center, principal investigator of a clinical study testing a drug that may prevent cancer metastasis, with Vanderbilt drug repurposing program team members Robert Lavieri, PhD, and Meghan Joly, PhD. (photo by Joe Howell)

A clinical study of a drug that may block cancer metastasis is currently enrolling patients at the Vanderbilt-Ingram Cancer Center.

The study will test the drug ifetroban in patients who have completed cancer treatment for one of five cancer types and have no evidence of disease, but who are at very high risk for cancer recurrence.

“Patients who have completed their treatment course rely on ‘watchful waiting’ for clinical evidence of cancer recurrence,” said Ingrid Mayer, MD, MSCI, Ingram Professor of Cancer Research and principal investigator of the ifetroban study. “Our goal is to develop therapies that directly target tumor cell metastasis and that change the watchful waiting into a time of proactive prevention.”

The ifetroban study is one of multiple projects resulting from the drug repurposing program launched in 2016 by the Vanderbilt Institute for Clinical and Translational Research (VICTR). The drug repurposing team uses human genetic data from BioVU, Vanderbilt’s DNA biobank linked to de-identified electronic health records, to find new indications for drugs that are already approved or that have passed phase I/II clinical safety studies. The program is intended to accelerate the pace of clinical drug development.

Ifetroban is an investigational drug that was developed for cardiovascular diseases and is currently being evaluated in a series of phase II trials unrelated to oncology. It blocks the activity of the thromboxane A2 receptor, part of the broad arachidonic acid signaling cascade.

The idea that ifetroban might be useful for preventing cancer metastasis started with the discovery in BioVU of an association between a genetic variant that increases thromboxane A2 receptor activity and increased metastasis of multiple primary cancers. The finding suggested that blocking thromboxane A2 activity might prevent or reduce metastasis.

Drug repurposing team members strengthened the case with a literature review that identified existing studies linking arachidonic acid signaling and cancer. They then partnered with Rebecca Cook, PhD, associate professor of Cell and Developmental Biology, to study ifetroban in mouse models of various cancers. Cook and her colleagues found that ifetroban prevented or delayed metastasis of different cancer types and that it appeared to act on blood vessels rather than directly on tumor cells.

The current pilot study will enroll 60 patients who have been treated for pancreatic, lung, stomach, esophageal or triple-negative breast cancer and have no evidence of active disease after completion of their treatment. The patients will be randomized to take an oral ifetroban or placebo pill once a day for a year.

Because ifetroban has not been previously tested in patients with cancer, the pilot study will primarily assess safety and tolerability, but will allow investigators to have a preliminary idea if the treatment works to prevent metastasis.

The study team hopes that more people who take the drug are alive and recurrence-free after one year. The team is also applying for funding for a large multi-site phase II trial of ifetroban for cancer metastasis prevention.

“This study is a powerful example of how the drug repurposing program is meeting its goal of speeding up the drug development process,” said Gordon Bernard, MD, director of VICTR and Executive Vice President for Research at Vanderbilt University Medical Center. “Repurposing of drugs never before tested in cancer offers exciting opportunities for future cancer drug development.”

In addition to Mayer, Dana Cardin, MD, MSCI, assistant professor of Medicine, and Leora Horn, MD, Ingram Associate Professor of Cancer Research, are co-investigators in the trial, focusing on the gastrointestinal and lung cancer patient populations, respectively. This trial is being supported by the VICC and its Clinical Trials Shared Resource. Cumberland Pharmaceuticals Inc. owns the license for ifetroban and provides the study drug to Vanderbilt to evaluate for cancer-related indications.