CompletedPhase 1

Dose Finding Trial of MK-7075 in Children and Adults With Proteus Syndrome

United States6 participantsStarted 2015-11-16

Plain-language summary

Background: Proteus syndrome (PS) is caused by a mutation in the AKT1 gene. This gene makes a protein that communicates with other proteins in the body to make cells grow. The AKT1 mutation changes chemical signals in the body and causes overgrowth. PS can be fatal. The drug MK-7075 reduces signals from the AKT1 protein. This may reduce or stabilize some of the overgrowth in people with PS. Researchers want to find the best dose of MK-7075 based on its effect on tissues in people with PS. Objective: To determine the safety, tolerability, and recommended dose of MK-7075 in people with PS. Eligibility: People ages 6 and older with PS Design: Participants will be screened with medical history, physical exam, and blood and urine tests. Participants will take MK-7075 by mouth once daily for up to 12 28-day cycles. Participants must stay near the NIH Clinical Center (CC) during the whole first cycle, for weekly visits to the CC. For cycle 2, they will have visits every 2 weeks. They will have 1 visit before cycles 3 and 4, and once before every other cycle for cycles 5 11. The final visit will be at the end of cycle 12. Visits may include: Small skin samples taken. ECG: Soft electrodes on the skin record heart signals. Echocardiogram: A small probe held to the chest takes pictures of the heart. MRI: Participants will lie in a machine that takes pictures of the body. Joint and mobility function tests. Participants will complete surveys by phone and in person. Participants will keep a daily medication and symptom diary. ...

Who can participate

Age range6 Years – 65 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

* INCLUSION CRITERIA: * Meets published clinical criteria for PS. * Measurable disease: Patients must have at least one measurable lesion for volumetric MRI or photographic CCTN. * Has a CLIA-validated report demonstrating presence of a mosaic AKT1 c.49G\>A mutation. * 6 years of age or older. The age limits including children and adolescents were chosen because childhood and puberty are considered to be the greatest risk for disease progression, and MK-7075 may provide the most benefit to this young group of patients. In addition, an important objective of this study is to characterize the pharmacokinetics of MK-7075 in the pediatric population since it has been better studied in adults. * Not using nor has used within the past 6 months any medication known to affect the AKT/PI3K pathway (e.g., everolimus), reviewed by NIHCC pharmacist. * Performance status: Patients greater than or equal to 16 years of age must have a Karnofsky performance level of greater than or equal to 40%, and adolescents 6 - 16 years old must have a Lansky performance of greater than or equal to 40%. * Is willing to identify and allow us to communicate with an outside medical provider if needed. * Hepatic function: Bilirubin must be less than or equal to 1.5 x the upper limit of normal and the SGPT (ALT) must be less than or equal to 2.5 x the upper limit of normal. * Cardiac function: Must have an ejection fraction with normal limits for age by echocardiogram. * Must have cognitive abilities to compl…

What they're measuring

Tissue drug levels

Timeframe: End of cycle 3

Tissue phospho-AKT level

Timeframe: End of cycle 3

Tolerabilty/Side Effects

Timeframe: Ongoing

Trial details

NCT IDNCT02594215

SponsorNational Human Genome Research Institute (NHGRI)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2017-12-31