RECRUITING

MK-7075 (Miransertib) in Proteus Syndrome

Conditions

Proteus Syndrome AKT1 CCTN Mosaic Overgrowth Disorder

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: To learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome. Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20-30 visits at the NIH.

Official Title

A Multi-Cohort Phase 2 Dose-Escalation Study of MK-7075 (Miransertib) in Proteus Syndrome

Quick Facts

Study Start:2022-05-20

Study Completion:2028-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04316546

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Years to 99 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Signed informed consent, and when applicable, signed assent * Have a molecular diagnosis of Proteus syndrome with documented somatic AKT1 mutation from a CLIA-certified laboratory or international equivalent. * Have progressive and measurable disease (e.g., a measurable manifestation of Proteus syndrome with evidence or report of worsening of manifestation(s)/ in the last 12 months) * Adequate organ function as indicated by the following laboratory values: * Hemoglobin (Hgb): \>=10.0 g/dL * Glycated hemoglobin (HbA1c): \<=8% (\<=64 mmol/mol) * Absolute neutrophil count (ANC): \>=1.5 x 10\^9/L * Platelet count \>=150 x 10\^9/L 1. Total bilirubin \<=2 x upper limit of normal (ULN) 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 x ULN 1. Serum creatinine depending on age: * Cholesterol: \<=400 mg/dL (\<=10.34 mmol/L) * Triglyceride: \<=500 mg/dL (\<=5.7 mmol/L) * If a female is of child-bearing potential, documentation of a negative pregnancy test is required prior to enrollment. Sexually active participants (male and female) must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse while on study and for up to 90 days after ending treatment * Ability to complete the questionnaires by the participant and/or his/her caregiver * Individuals without an evaluable plantar CCTN * No prior exposure to miransertib * Male or female participants age \>=3 years old and BSA of \>=0.33 m\^2	* Any experimental systemic therapy for the purpose of treating Proteus syndrome (e.g., sirolimus, everolimus, high dose steroids, alpelisib) within two weeks of the first dose of miransertib, except for participants who were previously or are currently treated with miransertib under a Compassionate Use/Expanded Access program or existing protocol * Participants who were previously treated with or currently are receiving miransertib will be enrolled on Cohort 3 and treated according to the Schedule of Assessments/Study Visits defined in this protocol * Intolerance of, or severe toxicity attributed to, AKT inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib) * Concurrent severe uncontrolled illness not related to Proteus syndrome * Ongoing or active infection * Known human immunodeficiency virus (HIV) infection malabsorption syndrome * Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements * Pregnant or breastfeeding (contraception requirements can be found above and in the informed consent form) * Inability to comply with study evaluations or to follow drug administration guidelines * Concomitant use of a prohibited medication * Regular tobacco use and/or use of cannabidiol/tetrahydrocannabidiol (CBD/THC), and/or vaping products

Inclusion Criteria

Exclusion Criteria

* Signed informed consent, and when applicable, signed assent
* Have a molecular diagnosis of Proteus syndrome with documented somatic AKT1 mutation from a CLIA-certified laboratory or international equivalent.
* Have progressive and measurable disease (e.g., a measurable manifestation of Proteus syndrome with evidence or report of worsening of manifestation(s)/ in the last 12 months)
* Adequate organ function as indicated by the following laboratory values:
* Hemoglobin (Hgb): \>=10.0 g/dL
* Glycated hemoglobin (HbA1c): \<=8% (\<=64 mmol/mol)
* Absolute neutrophil count (ANC): \>=1.5 x 10\^9/L
* Platelet count \>=150 x 10\^9/L
1. Total bilirubin \<=2 x upper limit of normal (ULN)
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 x ULN
1. Serum creatinine depending on age:
* Cholesterol: \<=400 mg/dL (\<=10.34 mmol/L)
* Triglyceride: \<=500 mg/dL (\<=5.7 mmol/L)
* If a female is of child-bearing potential, documentation of a negative pregnancy test is required prior to enrollment. Sexually active participants (male and female) must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse while on study and for up to 90 days after ending treatment
* Ability to complete the questionnaires by the participant and/or his/her caregiver
* Individuals without an evaluable plantar CCTN
* No prior exposure to miransertib
* Male or female participants age \>=3 years old and BSA of \>=0.33 m\^2

* Any experimental systemic therapy for the purpose of treating Proteus syndrome (e.g., sirolimus, everolimus, high dose steroids, alpelisib) within two weeks of the first dose of miransertib, except for participants who were previously or are currently treated with miransertib under a Compassionate Use/Expanded Access program or existing protocol
* Participants who were previously treated with or currently are receiving miransertib will be enrolled on Cohort 3 and treated according to the Schedule of Assessments/Study Visits defined in this protocol
* Intolerance of, or severe toxicity attributed to, AKT inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib)
* Concurrent severe uncontrolled illness not related to Proteus syndrome
* Ongoing or active infection
* Known human immunodeficiency virus (HIV) infection malabsorption syndrome
* Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
* Pregnant or breastfeeding (contraception requirements can be found above and in the informed consent form)
* Inability to comply with study evaluations or to follow drug administration guidelines
* Concomitant use of a prohibited medication
* Regular tobacco use and/or use of cannabidiol/tetrahydrocannabidiol (CBD/THC), and/or vaping products

Contacts and Locations

Study Contact

Christopher A Ours, M.D.

CONTACT

(301) 443-8750

chris.ours@nih.gov

Leslie G Biesecker, M.D.

CONTACT

(301) 402-2041

lesb@mail.nih.gov

Principal Investigator

Leslie G Biesecker, M.D.

PRINCIPAL_INVESTIGATOR

National Human Genome Research Institute (NHGRI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Human Genome Research Institute (NHGRI)

Leslie G Biesecker, M.D., PRINCIPAL_INVESTIGATOR, National Human Genome Research Institute (NHGRI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-05-20

Study Completion Date2028-03-31

Study Record Updates

Study Start Date2022-05-20

Study Completion Date2028-03-31

Terms related to this study

Keywords Provided by Researchers

AKT1
CCTN
Mosaic Overgrowth Disorder

Additional Relevant MeSH Terms

Proteus Syndrome