Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations

Boston Children's Hospital

Status and phase: Begins enrollment in 1 month; Phase 3; Phase 2

Conditions: Riley Smith Syndrome; PTEN Hamartoma Tumor Syndrome; Lhermitte-Duclos Disease; Bannayan Riley Ruvalcaba Syndrome; Myhre Riley Smith Syndrome; Cowden's Syndrome; Cerebellum Dysplastic Gangliocytoma; Bannayan Zonana Syndrome; Cowden's Disease

Treatments: Drug: Everolimus blinded oral capsules; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT07218575

IRB-P00049577

109110 (Other Identifier)

Details and patient eligibility

About

The goal of this study is to examine the safety and treatment effects of everolimus in adults and children with PTEN Hamartoma Tumor Syndrome (PHTS) who experience social difficulties. The study will measure if everolimus can safely improve social abilities and functioning in this study population.

PTEN Hamartoma Tumor Syndrome (PHTS) is a genetic condition that results from alteration (germline variant) to the PTEN gene. It is associated with a wide range of symptoms and characteristics, which vary from individual to individual. These include symptoms such as harmatomas (non-cancerous lesions), an increased risk of certain types of cancer, having a larger than average head, and abnormalities in blood vessels. Some people also have neurobehavioral problems including social difficulties. It is estimated approximately 25% (1 in 4) of people with PHTS meet the criteria for an autism diagnosis.

The study lasts for one year. In the first 6 months half of participants will receive everolimus as a once daily oral tablet, and half will receive placebo tablets. For the second 6 months all participants will receive everolimus. Visits to the study clinic are required at the start, month 3, month 6, month 9 and month 12, with phone calls or virtual visits in between. Assessments include questionnaires, blood tests and urine tests, physical and neurological exams, and vital signs.

Everolimus is an existing FDA approved medication used to treat other conditions, including a genetic condition called tuberous sclerosis complex which has some similarities to PHTS, and several types of cancer.

Enrollment: 60 estimated patients

Sex: All

Ages: 5 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of PTEN Harmartoma Tumor Syndrom (PHTS), confirmed by genetic testing (the testing may be done as part of study screening)
2. Experiences at least moderate levels of social difficulties, based on SRS T score > 60 (measured during screening Have at least a moderate impairment in social abilities, based on SRS score during study screening
3. Fluent in English
4. Females of child-bearing potential must have no plans to become pregnant and be using contraception during the study (if sexually active).
5. Availability of parent, care-giver, partner or other suitable individual who can provide observation reports and provide transportation to attend clinic visits
6. Adequate liver, kidney and bone-marrow function (checked during screening)
7. Medically stable
8. No plans to change school, behavioral therapies, home services or speech therapy during the study period
9. Ability to swallow medicine in pill form

Exclusion criteria

1. Ongoing or planned treatment with any medication with known or possible ant-mTOR activity (e.g. sirolimus), or strong inducers or inhibitors of CYP3A, CYP2D6, P450 or PgP (e.g. cyclosporine, ketoconazole, erythromycin, rifampin, phenytoin, phenobarbital) or ACE inhibitors
2. Chronic treatment with systemic corticosteroids or other immunosuppressive treatments (topical or inhaled corticosteroids are allowed).
3. Major surgery or any anti-cancer therapies (including radiotherapy) within 4 weeks of enrollment
4. Neurosurgery within 6 months of enrollment
5. Uncontrolled diabetes defined as HbA1c >8% despite treatment
6. Uncontrolled hyperlipidemia (defined as fasting serum cholesterol > 300 mg/dL OR >7.75 mmol/L AND fasting triglycerides > 2.5 x ULN, assessed during screening)
7. History of Hepatitis B, Hepatitis C or HIV
8. Participation in a clinical trial in the 60 days prior to study entry
9. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
10. Patients who have a history of another primary malignancy, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from with the patient has been disease free for > 3 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups, including a placebo group

Everolimus

Experimental group

Description:

Everolimus, oral capsules once daily for 12 months; initiated at 2.5mg/day and then increased every 2-3 weeks until a therapeutic blood level is achieved

Treatment:

Drug: Everolimus blinded oral capsules

Placebo

Placebo Comparator group

Description:

Placebo matched to everolimus oral capsules once daily for 6 months, Initiated at 1 tablet per day and then increased every 2-3 weeks to maintain blind. Then Everolimus, oral capsules once daily for 6 months

Treatment:

Drug: Placebo