Early clinical research by Vanderbilt Health and Cumberland Pharmaceuticals Inc. suggests that an investigational drug originally developed to treat cardiovascular disease may reduce the risk of metastasis — or spread — of breast, lung and other solid tumors.

The pilot clinical trial of 29 patients with solid tumors at high risk of early metastatic recurrence confirmed that ifetroban, a thromboxane A2 receptor antagonist, was safe and well tolerated, and supported further development of the drug to prevent cancer metastasis.

While not statistically powered for efficacy, the randomized, double-blind, and placebo-controlled Phase 2a clinical trial also compared the percentage of patients who experienced a distant metastatic recurrence 12 months after completion of the study.

Seventeen percent of participants who received ifetroban experienced a distant metastatic recurrence, compared to 50% of those who received an inactive placebo. No deaths due to distant metastatic disease occurred among those who received ifetroban, while three deaths occurred in the placebo group.

“We are encouraged that ifetroban demonstrated a favorable safety profile in this patient population and the potential efficacy trends are promising, supporting further clinical development,” said Cumberland Pharmaceuticals Chief Executive Officer A.J. Kazimi.

Cumberland Pharmaceuticals is a Nashville-based specialty pharmaceutical company focused on developing new products for rare diseases.

“A therapeutic intervention aimed at metastasis prevention for cancer patients with high risk of recurrence that is given during the period of ‘watchful waiting’ could be groundbreaking if proven beneficial in larger scale investigations,” said Ben Ho Park, MD, PhD, the Benjamin F. Byrd Jr. Professor of Oncology, professor of Medicine, and director of Vanderbilt-Ingram Cancer Center.

The study is a project of Vanderbilt Health’s Drug Repurposing program, which was established in 2016 under the Vanderbilt Institute for Clinical and Translational Research (VICTR).

The program uses human genetic data from BioVU, Vanderbilt Health’s DNA biobank, which is linked to de-identified electronic health records, to find new indications for drugs that are already approved or have passed Phase 1 and Phase 2 clinical safety studies. For example, the drug repurposing team has found that adding guanfacine, a drug used to treat high blood pressure, to routine trigeminal nerve block injections can enhance pain relief in patients with trigeminal neuralgia, intense, sudden facial pain.

Earlier this year, they reported that EG501, an investigational drug developed by Evergreen Therapeutics Inc. which targets a receptor in the brain involved in learning and memory, improved cognitive function in patients with lupus, an auto-immune disease.

For the past 20 years, Vanderbilt Health researchers have been studying ifetroban for its potential to treat conditions ranging from fibrotic lung disease to heart failure in patients with Duchene muscular dystrophy.

The thromboxane A2 receptor plays a variety of roles in different cell types throughout the body, including the activation and aggregation of platelets, a type of blood cell involved in clotting. In turn, malignant cells that escape cancer treatment can stick to platelets and “ride” to distant parts of the body.

A phenome-wide association study (PheWAS) of BioVU’s genetic and health records database conducted by Vanderbilt Health investigators linked a variant in the receptor gene to an increased risk of metastatic disease across multiple primary cancers.

Preclinical studies demonstrated that ifetroban reduced metastasis in several animal models without affecting tumor growth.

By blocking platelet activation and aggregation through its action on the thromboxane A2 receptor, ifetroban is thought to limit the ability of tumor cells to migrate across blood vessel walls, invade other organs, and evade detection by the immune system.

After completing cancer therapy, patients at high risk of recurrence who were enrolled in the clinical trial received daily oral doses of ifetroban or placebo for 12 months, then were followed for another 12 months.

Kazimi praised the contributions of the Vanderbilt Health research team, which he said, “have been essential to this advance in oncology patient care.”

Results of this study will be used to guide the design of larger human trials verifying efficacy and further demonstrating safety.

“We look forward to pursuing those pivotal studies as we relentlessly look for treatments to benefit patients living with cancer,” Park said.

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Susan G. Komen has awarded $10.8 million in new research grants that will help propel innovative science and deliver hope to those facing breast cancer. The grant recipients include three researchers from Vanderbilt University Medical Center.

The grants support 25 cutting-edge projects at 17 institutions — marking a powerful commitment to improving outcomes for people living with breast cancer today and in the future.

“We are proud to support these exceptional researchers who are pushing the boundaries of what’s possible in breast cancer science,” said Paula Schneider, president and CEO of Susan G. Komen. “Research saves lives, and now more than ever, we must invest in science that brings hope to patients — especially those facing the most aggressive forms of breast cancer.”

The three VUMC researchers were each awarded Komen Leadership Grants of $400,000. The Komen Leadership Grant Program supports innovative, hypothesis-driven breast cancer research that aligns with Komen’s mission to save lives and improve personalized care and outcomes for all. Open to Komen’s Scientific Advisors and to Komen Scholars, the program funds bold, high-risk/high-reward projects with the potential to significantly advance the field of breast cancer research.

The VUMC recipients are Tuya Pal, MD, Ingram Professor of Cancer Research and professor of Medicine; Ben Ho Park, MD, PhD, Benjamin F. Byrd Jr. Professor of Oncology and professor of Medicine; and Jennifer Pietenpol, PhD, Ingram Professor of Cancer Research and professor of Biochemistry.

Through this research investment, Komen is prioritizing the most pressing challenges facing patients, including metastatic breast cancer, optimal health for all and the need for more precise, personalized treatment strategies to improve care and outcomes for everyone impacted by breast cancer.

“Komen’s commitment to breast cancer research comes at a pivotal time and will drive meaningful advances in our understanding of the disease and care of patients,” said Ann Partridge, MD, MPH, Chief Scientific Advisor for Komen. “By fueling science that is both innovative and inclusive, we’re accelerating progress where patients need it most — while building a foundation for individualized care for all.”

Komen is the largest nonprofit funder of breast cancer research outside the U.S. government, investing nearly $1.1 billion since its inception. Unlike many research institutions, Komen’s work is powered entirely by the generosity of individual donors, corporate partners and community supporters.

“Investing in top scientific talent is one of the most powerful ways we can drive progress,” said Pietenpol, PhD, Chief Scientific Advisor for Komen. “Komen’s commitment, especially to early-career researchers, cultivates a vibrant ecosystem where bold ideas and pioneering research can thrive, accelerating our path toward the cures we urgently seek.”

Pietenpol holds the Brock Family Directorship in Career Development at VUMC. Park is director of the Vanderbilt-Ingram Cancer Center and a member of the Komen Scientific Advisory Board. Pal is a Komen Scholar.

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