Case study: Clinical trials of existing medications
Introduction
PHTS is caused by an alteration in the PTEN gene, which results in the disruption of an important pathway in our cells, called PI3K, which is responsible for keeping cell division under control. This same pathway is also important for other conditions, including some non-inherited cancers, and there are existing medicines that act on this pathway that are already being used to treat people with certain cancers. However, no drugs have yet been approved by health authorities for treating PHTS.
PTEN Research, with others, funded exploratory clinical trials of two different medicines, everolimus and sirolimus, that are known to inhibit the PI3K pathway. Both studies looked at both the safety and the activity of these medications in people with PHTS.
We hope to announce new clinical trials in 2026.
Project 1 key facts
Project title: RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
Type of study: Clinical trial (NCT02991807)
Lead researcher: Prof Mustafa Sahin
Institution: Boston Children’s Hospital, USA
Project start: June 2017 Completed: December 2021
Project 1 goals
Professor Mustafa Sahin, together with colleagues at Stanford University in California and the Cleveland Clinic in Ohio, studied whether a medicine called everolimus was able to improve the cognitive difficulties that commonly occur in PHTS. These difficulties include things like problems with the amount of information an individual can hold in their short-term memory, or how long it takes to do a mental task.
Project 1 overview
In total, 46 children and adults aged 5-45 years who have PHTS with cognitive symptoms were enrolled into this clinical trial. Each received 6 months of study treatment.
Half of those taking part received everolimus, and half received dummy medicine that looks like everolimus, called placebo. This is a typical approach in clinical trials to help understand if the treatment is really working when comparing the improvement of those receiving the real medication compared to the dummy.
Project 1 outcomes
This trial was completed in December 2021. The results show that everolimus was well tolerated but further studies are needed to better understand if it is truly safe and effective.
The following publications have resulted from work associated with this grant:
- A randomized double-blind controlled trial of everolimus in individuals with PTEN mutations: Study design and statistical considerations
- A randomized controlled trial of everolimus for neurocognitive symptoms in PTEN hamartoma tumor syndrome
- Sensitivity Analysis of the Efficacy of Everolimus for Neurocognitive Symptoms in PTEN Hamartoma Tumor Syndrome
Project 2 key facts
Project title: Sirolimus for Cowden Syndrome With Colon Polyposis
Type of study: Clinical trial (NCT04094675)
Lead researcher: Dr Peter Stanich
Institution: Ohio State University, USA
Project start: August 2019 Completed: June 2025
Project 2 goals
Dr Peter Stanich conducted a study of a medicine called sirolimus in people with PHTS to see if, over a year, it could reduce the number of small growths (polyps) of non-cancerous tissue in the lower part of the digestive tract.
Project 2 overview
This trial recruited 5 out of 10 planned participants. Two of the participants completed the full one-year treatment period.
Project 2 outcomes
This trial was completed in June 2025. The number of polyps reduced for the two participants who completed the study. Side effects may limit usage as two participants had side effects that were likely related to the sirolimus treatment.
Larger studies are required to better understand if sirolimus may be helpful for individuals with PHTS and polyps in the digestive tract.
The following publication resulted from work associated with this grant:
· Sirolimus for Colon Polyposis in PTEN Hamartoma Tumor Syndrome