Trials to Study Use of 2 Cancer Drugs in Patients With Lymphatic Malformations

Genetic changes are similar between some vascular anomalies and cancers

Smiling child in green shirt with superimposed outline of the lymphatic system

The Vascular Anomalies Program at Cleveland Clinic Children’s is preparing to begin two clinical trials studying the use of common cancer drugs in the treatment of children and adults with lymphatic malformations.


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While most vascular anomalies programs serve only pediatric patients, the program at Cleveland Clinic Children’s serves patients throughout their life span. That distinctly positions Cleveland Clinic Children’s to understand how the diseases change over a developmental spectrum, says team member Michael Kelly, MD, PhD, a pediatric hematologist-oncologist.

Cleveland Clinic Children’s Vascular Anomalies Program serves patients affected by malformations of the vascular and lymphatic systems and the associated tumors. Except for relatively common hemangiomas, these malformations are rare, affecting approximately 1 in 4,000 individuals. They also typically have a progressive disease course and frequently affect a patient’s quality of life.

“In our program, we offer a comprehensive care approach with teams of physicians from different disciplines, such as dermatology, oncology, interventional radiology and reconstructive surgery,” says Dr. Kelly. “We see patients every month in this comprehensive care setting and also see them independently, based on their needs.”

Patients affected by vascular anomalies often have multiple conditions caused by the underlying disease, he adds. Treating all resulting physical and mental health issues requires a comprehensive approach.

“We are in the process of developing a database for our program to better understand the range of patients that we’re seeing,” Dr. Kelly says. “Then we’re going to start some interventional clinical trials to offer our patients leading-edge therapies.”

Understanding the genetics of vascular anomalies

One active area of research globally is the genetics of vascular anomalies.


Researchers have found genetic underpinnings for all of these diseases, notes Dr. Kelly. Lymphatic malformations have been linked to a series of somatic mutations that occur in genes during development.

“Those genetic changes are often very similar to what we find in both pediatric and adult cancers,” he says. “This understanding has allowed us to work on repurposing medications developed to treat cancer for use in patients with vascular anomalies.”

Alpelisib for patients with lymphatic malformations

In line with these efforts, Cleveland Clinic Children’s is planning two clinical trials.

The first trial will study the efficacy, safety and pharmacokinetics of alpelisib in pediatric and adult patients with lymphatic malformations associated with the PIK3CA mutation. Studies have shown that approximately 20% to 30% of patients with lymphatic malformations have the PIK3CA mutation.

“Alpelisib was designed for patients with breast cancer who have a particular genetic change, and that genetic change is also seen in a variety of vascular malformations,” Dr. Kelly says. “We are now preparing to study how effective alpelisib is in these patients, not only on their disease state but also on symptom control and quality of life.”

Topical rapamycin for patients with cutaneous lymphatic malformations

The second trial will test the safety and effectiveness of a topical rapamycin formulation in patients with cutaneous lymphatic malformations. Rapamycin is a potent immunosuppressant used to prevent organ rejection in patients after transplantation as well as to treat certain types of cancer.


“When patients have lymphatic malformations with skin involvement, the growths can leak fluid that irritates skin and, more importantly, causes recurrent infections,” Dr. Kelly explains. “So, treating these skin lymphatic malformations can significantly improve patients’ overall quality of life.”

The idea that rapamycin could be effective in patients with lymphatic malformations came from the observation that these patients express high levels of mammalian target of rapamycin (mTOR). The findings from an earlier trial of systemic (oral) rapamycin in this patient population showed that many responded well to this treatment.

“We hope these trials will be the first of many by our program,” says Dr. Kelly. “We want to lead the field in offering novel treatments that improve the quality of life for patients with vascular and lymphatic malformations.”

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