RAD001 and Neurocognition in PTEN Hamartoma Tumor Syndrome
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|ClinicalTrials.gov Identifier: NCT02991807|
Recruitment Status : Active, not recruiting
First Posted : December 14, 2016
Last Update Posted : August 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|PTEN Gene Mutation PTEN Hamartoma Tumor Syndrome||Drug: RAD001 Drug: Placebo||Phase 1 Phase 2|
This is a signal seeking Phase I/II 6-month, randomized, double-blind placebo-controlled trial of everolimus in individuals, ages 5 to 45 years with a PTEN mutation, with safety and neurocognition as the primary endpoints.
Participant's or a legal guardian will need to sign an informed consent prior to enrollment in the study. To determine eligibility participants will undergo a series of screening tests and safety measures. If determined to be eligible for the blinded phase of the study, participants will be randomly assigned to take either the study drug or a placebo (pill with no medicine).
The blinded phase of the study involves about eight visits, five of which will occur at the study site, and three of which will be conducted over the phone. These visits will take place over a six month period. Study visits will vary in length. Baseline, three month and six month visits may last up to 8 hours, if optional measures are done, while all other visits will be less than 2 hours. The study visits include blood draws, general health exams, and neuropsychological assessments. The study will also include optional eye-tracking, EEG and auditory evoked potential (AEP) measures, and the collection of microbiome/mycobiome and biomarker blood sample. There is no fee to participate in this study. The study drug will be provided at no charge during the study.
After the 6 month treatment phase, individuals who were randomly assigned to take placebo will be offered inclusion in a 6 month open label phase where the study drug will be provided at no charge. The open label phase assessments will be similar to those done in the blinded phase, but patients/families will only need to return to the study site three times during this phase.
Participants will receive a developmental assessments report after completing the study. After all study data has been analyzed, patients and families will also be informed of the overall results. Treatment on this study may or may not improve an individual's learning skills (neurocognition) or behavior. We hope that future patients and families will benefit from what is learned by this study.
Specific Aims /Objectives Primary objective
-To evaluate the safety of everolimus compared with placebo in patients with PTEN mutations focusing on NCI CTCAE Grade 3 and 4 adverse events, serious adverse events, and Grade 3 and 4 laboratory toxicities.
-To evaluate the efficacy of everolimus on neurocognition and behavior in inividuals with PTEN mutations compared to placebo as measured by standardized, direct and indirect neurocognitive tools and behavioral measures.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Official Title:||A Randomized Double-Blind Controlled Trial of Everolimus in Individuals With PTEN Mutations (RAD001XUS257T)|
|Actual Study Start Date :||June 12, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
RAD001 is formulated as tablets of 5.0 mg or 2.5mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis.
RAD001 is formulated as tablets of 5.0 mg strength, blister-packed under aluminum foil in units of 10 tablets and dosed on a regular basis. RAD001 tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive.
Patients will be instructed to take 4.5 mg/m2 of RAD001 orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast.
Placebo Comparator: Placebo
Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10.
Matching placebo will be provided as a matching tablet and will also be blister packed under aluminum foil in units of 10. Matching placebo tablets should be opened only at the time of administration as drug is both hygroscopic and light-sensitive.
Patients will be instructed to take 4.5 mg/m2 of the matching placebo orally with a glass of water at regular intervals at the same time (delete: each day) in the morning after a light, nonfat breakfast.
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: Through study completion, an average of 6 months ]The primary endpoint will be safety as measured by study drop-out rate due to side effects, comparing everolimus vs. placebo. We will also determine the frequency of adverse events by type and severity.
- Change in Working Memory at 6 Months [ Time Frame: 6 months ]Working memory will be evaluated using the Stanford Binet 5 or Mullen Scales of Early Learning at 6 months
- Change in Processing Speed at 6 Months [ Time Frame: 6 months ]Processing speed will be evaluated using mean reaction time on the Conner's Continuous Performance Test (CPT)-3.
- Change in Fine Motor Skills at 6 Months [ Time Frame: 6 months ]Fine motor skills will be evaluated using the Purdue Pegboard sub-tests average of both hands
- Change in Attention at 6 Months [ Time Frame: 6 months ]Attention will be measured by Conners' Continuous Performance Test - 3 - Discriminability index (d') and Omissions
- Change in Impulsivity at 6 Months [ Time Frame: 6 months ]Impulsivity will be measured by Conners' Continuous Performance Test-3- Commissions and Bias (B').
- Change in Global Cognitive Ability at 6 Months [ Time Frame: 6 months ]Change in global cognitive ability will be measured by Stanford-Binet 5 or Mullen; Full scale, verbal and nonverbal ability (IQ)
- Change in Motor Functioning at 6 Months [ Time Frame: 6 months ]Motor functioning will be measured by the Purdue Pegboard (Pegs): Dominant and non-dominant hand combined standard scores and Developmental Coordination Disorder Questionnaire (DCDQ): Total score.
- Change in Communication Ability at 6 Months [ Time Frame: 6 months ]Communication ability will be measured by using standard scores of the Peabody Picture Vocabulary Test (PPVT-4), Expressive Vocabulary Test (EVT-2)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02991807
|United States, California|
|Palo Alto, California, United States, 94305|
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Ohio|
|Cleveland, Ohio, United States, 44104|
|Principal Investigator:||Mustafa Sahin, MD, PhD||Boston Children's Hospital|