Currently, no therapeutic interventions are approved for PHTS, however, a limited number of clinical trials have been undertaken using drugs approved for other conditions. Below, we have collected clinical trials and case series in which PHTS or Cowden syndrome patients were enrolled.
Active clinical trials
Official title: Sirolimus for Cowden Syndrome With Colon Polyposis (NCT04094675)
Status: Ongoing
This phase II, open-label, pilot trial aims to determine whether treatment with sirolimus can reduce colon polyps in patients with a PTEN germline mutation (estimated enrolment n=10). This project is receiving funding from PTEN Research.
Official title: Phase III multicentric study evaluating the efficacy and safety of sirolimus in Vascular Anomalies that are refractory to standard care (VASE) (NCT02638389)
Status: Ongoing
This phase III, open-label, single-arm trial started in January 2016 aims to enrol 250 patients to evaluate the efficacy and the safety of sirolimus to treat vascular malformations for which conventional therapies are ineffective or are considered high risk. An interim analysis (n=132, three of whom are PHTS patients) reported that sirolimus has a high efficacy and good tolerance in treatment of slow-flow vascular malformations in children and adults.
Official title: Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (SAFIR02_Breast) (NCT02299999)
Status: Active, not recruiting
The aim of this phase II, open-label, randomised trial is to use high throughput genome analysis as a therapeutic decision tool, to compare a targeted treatment administered according to the identified molecular anomalies of each patient's tumour. Exceptional response was observed in one patient with a germline PTEN mutation following treatment with the AKT inhibitor AZD5363/capivasertib.
Official title: A Study to Assess Safety and Tolerability, and Explore Efficacy of Leniolisib for Immune Dysregulation in Primary Immunodeficiency Disorders (NCT06549114)
Status: Ongoing
This study is an exploratory, non-randomized, open-label, within-patient dose escalation study. The primary objective is to assess safety and tolerability of leniolisib, a phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor, in patients diagnosed with genetically defined primary immunodeficiency (PID) disorders linked to PI3K signalling (including individuals with pathogenic variants in PTEN).
Completed/terminated clinical trials
Official title: A Pilot Study of Sirolimus (Rapamycin, Rapamune[Registered Trademark]) in Subjects With Cowden Syndrome or Other Syndromes Characterized by Germline Mutations in PTEN (NCT00971789)
Status: Completed
The aim of this phase I, open-label, single-arm trial was to inhibit the mTOR pathway and assess the impact on tissues presenting with pathology, including benign as well as malignant tumours. Sirolimus treatment was generally well tolerated in patients (n=18, all of whom had a PTEN germline mutation) with improvements seen in cerebellar function, skin lesions and GI polyps, with tumour assessment showing stable disease in the subset of patients with radiographically measurable disease.
Official title: A Phase 2 Study - Clinical Trial Assessing Efficacy and Safety of the mTOR Inhibitor Sirolimus in the Treatment of Complicated Vascular Anomalies (NCT00975819)
Status: Completed
The aim of this phase II, open-label, single-arm trial was to determine the effectiveness and safety of sirolimus in the treatment of children and young adults diagnosed with complicated vascular anomalies. The trial (n=61) included six PHTS patients, and showed that sirolimus was well tolerated, with significant improvement in patient quality of life reported.
Official title: A Randomized Double-Blind Controlled Trial of Everolimus in Individuals With PTEN Mutations (RAD001XUS257T) (NCT02991807)
Status: Completed
This phase II, randomised, double-blind, placebo-controlled trial of everolimus treatment in PHTS patients recruited individuals (n=46) aged 5 to 45 years to assess the safety and efficacy of everolimus on neurocognition and behaviour. Results showed that everolimus is well tolerated by PHTS patients and although the primary efficacy endpoint did not reveal improvement, several secondary efficacy endpoints moved in the direction of improvement. This project received funding from PTEN Research.
Official title: A Phase 2 Study of TAS-117 in Patients With Advanced Solid Tumors Harboring Germline PTEN Inactivating Mutations (NCT04770246)
Status: Terminated
The aim of this phase II, open-label, single-arm trial was two-fold; first to confirm the dose regimen of the allosteric AKT inhibitor TAS-117 in adult patients with solid tumours, irrespective of genetic mutation, followed by a second phase to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumour activity of TAS-117 in individuals with germline PTEN mutations with advanced or metastatic solid tumours (excluding primary brain tumours). Sixteen participants were included in the dose escalation portion of the trial prior to termination (one with a germline PTEN mutation). A durable clinical benefit associated with tumour shrinkage in one patient with a germline PTEN mutation and with metaplastic breast cancer was reported.
Official title: A Phase I/II Study of AZD5363 Combined With Paclitaxel in Patients With Advanced or Metastatic Breast Cancer. Comprising a Safety Run-In and a Placebo-controlled Randomised Expansion in ER+ve Patients Stratified by PIK3CA Mutation Status (BEECH) (NCT01625286)
Status: Completed
This phase I/II, quadruple-blind, randomised trial assessed the treatment of ER-positive breast cancer patients with the AKT inhibitor AZD5363/capivasertib, when in combination with paclitaxel. Exceptional response was observed in one patient with a germline and a second somatic PTEN mutation.
Official title: Clinical Study on Efficacy and Safety of the mTor Rapamycin Inhibitor Found in the Complex Vascular Malformations (NCT01811667)
Status: Completed
This phase II, open-label, single-arm study evaluated the efficacy and safety of sirolimus in 19 children and adults with vascular malformations (one of whom was a PHTS patient) for which conventional therapies, such as surgery or sclerotherapy, are ineffective or associated with high risk of complications. The results showed that sirolimus was well tolerated, enhanced quality of life and reduced pain.
