PTEN Gene MutationPhase 1/2NCT06080165
Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
A Phase 1/2 study testing Sirolimus in people with PTEN Gene Mutation and PTEN Hamartoma Tumor Syndrome, run by Stanford University at 3 sites in United States.
Trial summary
The goal of this study is to examine the safety and treatment effects of sirolimus for targeting social communication deficits in people with genetic disorders associated with PTEN germline mutations, which are often referred to as PTEN Harmartoma Tumor Syndrome (PHTS). Read more about this study
- Who is it for?
- Ages 5 to 45 years
- Conditions the study is for
- PTEN Gene Mutation, PTEN Hamartoma Tumor Syndrome, PTEN Hamartoma Syndrome
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 3 sitesUnited States
- Study dates
- Jul 2024to Jun 2028
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Inclusion Criteria: All participants will meet the following selection criteria:
- Male or female outpatients between 5.00 and 45.99 years of age
- PHTS confirmed by genetic testing;
- Fluent in English
- at least moderate severity of social skill deficits based on a social responsiveness scale t score ≥ 60
- Stable psychotropic and anti-epileptic medications for at least 4 weeks with the exception of fluoxetine which should be stable for at least 8 weeks
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- Adequate Liver function (SGOT, SGPT, TBili, Alk Phos all<3x normal); HCT>27%; WBC > 3.0, ANC >1,500, and platelets >100,000
- adequate renal function with a GFR ≥ 50 ml/min/m2 as determined by the Schwartz Formula for children and MDRD for adults (www.nkdep.nih.gov/professionals/gfr_calculators/index)
- Negative urine pregnancy test for females and no plans to become pregnant or conceive a child while participating in the study. The effects of mTOR inhibitors on the developing fetus at the doses used in this study are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study. Because of the possibility of drug interactions and the potential effect of female hormones on the growth of kidney angiomyolipomas and lymphangioleiomyomatosis, estrogen-containing oral contraceptives are not recommended in women enrolled in this study, so an effective non-estrogen or barrier method of contraception must be used.
- Medically stable with no active medical problems such as unstable seizures or cardiovascular disease or cancer that is not in remission as evidenced by medical history; -No anticipated changes in frequency and intensity of existing interventions such as behavioral and developmental treatments, in home services, or speech therapy;
- No planned changes in school placement in children and adolescents;
- Availability of reliable transportation to attend clinic visits;
- availability of a trustworthy informant who interacts with subject on a regular basis;
- Ability to participate in the testing procedures to the extent that valid standard scores and biological samples can be obtained.
Who cannot join
- Participants will be excluded if one of the following is met:
- Significant medical illness, such as endocrinopathies, cardiovascular disease, or severe chronic malnutrition;
- Pregnancy, planned pregnancy, or unwillingness to use adequate contraception;
- Planned changes to concomitant medications;
- Concomitant therapy, or prior use within 3 months of the baseline visit, with an agent with known or possible anti-mTOR activity or concomitant therapy with strong inhibitors (e.g., cyclosporine and ketoconazole) or inducers of CYP3A;
- Active infection at time of enrollment;
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- Participation in a clinical trial in the 30 days prior to study entry;
- Major surgery, radiation therapy or stereotactic radio-surgery within previous 4 weeks at time of enrollment; and
- Neurosurgery within prior 6 months at time of enrollment.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Cleveland Clinic
Cleveland, Ohio, 44195
Stanford University
Stanford, California, 94305
About this study
Official title: A Randomized Controlled Double-Blind Trial of Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
The goal of this study is to examine the safety and treatment effects of sirolimus for targeting social communication deficits in people with genetic disorders associated with PTEN germline mutations, which are often referred to as PTEN Harmartoma Tumor Syndrome (PHTS). The mechanism of sirolimus in the body has shown promise for helping to improve social communication skills in case reports of people with PHTS. Everolimus, a closely related compound, also showed benefits in social communication skills in a previous pilot trial in people with PHTS. This is a 6 month double-blind trial followed by at 6 month open label extension trial.
- Being tested
- Sirolimus, Placebo
- Keywords
- Sirolimus, Rapamune
- Medical subject headings
- Hamartoma Syndrome, Multiple
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune
Experimental: Sirolimus Participants that are 5 to 12.99 years old will start at 1 mg/m2/dose. Participants that are 13 to 45.99 years old and < 39.99 kg in weight will also start on 1 mg/day. Participants that are 13 to 45.99 years old and > 40 kg in weight will start on 2 mg/day. The target blood level will be 5-15 ng/ml with dose adjustment based on clinical labs of sirolimus levels. The target blood level will be 5-15 ng/ml with dose adjustment based on sirolimus levels obtained every 2 to 3 weeks after every dose change.
PlaceboDrug
matching placebo
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Participants that are 5 to 12.99 years old will start at 1 mg/m2/dose. Participants that are 13 to 45.99 years old and < 39.99 kg in weight will also start on 1 mg/day. Participants that are 13 to 45.99 years old and > 40 kg in weight will start on 2 mg/day. The target blood level will be 5-15 ng/ml with dose adjustment based on sirolimus levels obtained every 2 to 3 weeks after every dose change. Receives: Drug: Sirolimus |
| Placebo | Placebo comparator | matching placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in parent rated Social Responsiveness Scale, Second Edition Total Scores (SRS-2) total scores during treatment.
Measured: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Secondary outcomes (2)
Clinical Global Impression Improvement (CGI-I) Scale changes during treatment.
Measured: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Change from baseline on parent rated Stanford Social Dimensions Scale (SSDS)
Measured: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study startJul 2024 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Why it stopped: Investigator decided not to proceed with the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTEN Gene MutationStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Antonio Hardan, Stanford University
- Investigators
- Antonio Hardan, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06080165
- Sponsor's protocol ID
- IRB-72157
- Status last verified
- Jul 2024
- First submitted
- 29 Sep 2023
- Last updated
- 10 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be on the National Institute of Mental Health Data Archive (NDA).
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Double-Blind Trial of Sirolimus for Improving Social Abilities in People With PTEN Germline Mutations
- ClinicalTrials.gov ID
- NCT06080165
- Acronym / sponsor ID
- IRB-72157
- Keywords
- Sirolimus, Rapamune
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decided not to proceed with the trial.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- Jul 2024 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to examine the safety and treatment effects of sirolimus for targeting social communication deficits in people with genetic disorders associated with PTEN germline mutations, which are often referred to as PTEN Harmartoma Tumor Syndrome (PHTS). The mechanism of sirolimus in the body has shown promise for helping to improve social communication skills in case reports of people with PHTS. Everolimus, a closely related compound, also showed benefits in social communication skills in a previous pilot trial in people with PHTS. This is a 6 month double-blind trial followed by at 6 month open label extension trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusParticipants that are 5 to 12.99 years old will start at 1 mg/m2/dose. Participants that are 13 to 45.99 years old and < 39.99 kg in weight will also start on 1 mg/day. Participants that are 13 to 45.99 years old and > 40 kg in weight will start on 2 mg/day. The target blood level will be 5-15 ng/ml with dose adjustment based on sirolimus levels obtained every 2 to 3 weeks after every dose change. |
| Placebo | Placebo comparator | Drug: Placebomatching placebo |
Who may qualify
- Ages
- 5 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Inclusion Criteria: All participants will meet the following selection criteria:
- Male or female outpatients between 5.00 and 45.99 years of age
- PHTS confirmed by genetic testing;
- Fluent in English
- at least moderate severity of social skill deficits based on a social responsiveness scale t score ≥ 60
Key exclusion criteria (9 listed)
- Participants will be excluded if one of the following is met:
- Significant medical illness, such as endocrinopathies, cardiovascular disease, or severe chronic malnutrition;
- Pregnancy, planned pregnancy, or unwillingness to use adequate contraception;
- Planned changes to concomitant medications;
- Concomitant therapy, or prior use within 3 months of the baseline visit, with an agent with known or possible anti-mTOR activity or concomitant therapy with strong inhibitors (e.g., cyclosporine and ketoconazole) or inducers of CYP3A;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamuneExperimental: Sirolimus Participants that are 5 to 12.99 years old will start at 1 mg/m2/dose. Participants that are 13 to 45.99 years old and < 39.99 kg in weight will also start on 1 mg/day. Participants that are 13 to 45.99 years old and > 40 kg in weight will start on 2 mg/day. The target blood level will be 5-15 ng/ml with dose adjustment based on clinical labs of sirolimus levels. The target blood level will be 5-15 ng/ml with dose adjustment based on sirolimus levels obtained every 2 to 3 weeks after every dose change. | Drug | Sirolimus |
| Placebomatching placebo | Drug | Placebo |
Primary outcome
Change from baseline in parent rated Social Responsiveness Scale, Second Edition Total Scores (SRS-2) total scores during treatment.
Time frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
2 secondary outcomes
Clinical Global Impression Improvement (CGI-I) Scale changes during treatment.
Time frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Change from baseline on parent rated Stanford Social Dimensions Scale (SSDS)
Time frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Individual participant dataSharing planned: Yes. Data will be on the National Institute of Mental Health Data Archive (NDA).
Related trials for PTEN Gene Mutation
Active, not recruitingPhase 2
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Recruiting
An Intervention to Increase Genetic Testing in Families Who May Share a Gene Mutation Related to Cancer Risk and An Intervention to Help Patients and Their Primary Care Providers Stay Up-to-date About Uncertain Genetic Test Results
BRCA1 Mutation, POLD1 Gene Mutation
Not yet recruitingPhase 2/3
Double-Blind Trial of Everolimus for Improving Social Abilities in PTEN Germline Mutations
Cowden's Disease, Cowden's Syndrome
Active, not recruitingPhase 2
Testing GSK2636771 as a Potential Targeted Treatment in Cancers With PTEN Genetic Changes (MATCH-Subprotocol N)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Active, not recruitingPhase 2
Olaparib in Treating Patients With Metastatic Biliary Tract Cancer With Aberrant DNA Repair Gene Mutations
Bile Duct Adenocarcinoma, Fanconi Anemia Complementation Group Gene Mutation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Hardan, MD principal investigator
Stanford University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sirolimus in people with PTEN Gene Mutation and PTEN Hamartoma Tumor Syndrome, run by Stanford University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in parent rated Social Responsiveness Scale, Second Edition Total Scores (SRS-2) total scores during treatment. (time frame: Month 1, Month 2, Month 3, Month 4, Month 5, Month 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2024.