This study is currently recruiting participants.
Number
20-HG-0034
Sponsoring Institute
National Human Genome Research Institute (NHGRI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 3 Years Max Age: 99 Years
Referral Letter Required
No
Population Exclusion(s)
None
Keywords
AKT1; CCTN; Mosaic Overgrowth Disorder
Recruitment Keyword(s)
Condition(s)
Proteus Syndrome
Investigational Drug(s)
mk-7075 (miransertib)
Investigational Device(s)
Intervention(s)
Drug: MK-7075 (miransertib)
Supporting Site
National Human Genome Research Institute
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.
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INCLUSION CRITERIA: All participants in all Cohorts must meet the criteria below: -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. -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: Hematological: -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 Hepatic: a. Total bilirubin <=2 x upper limit of normal (ULN) b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 x ULN Renal: a. Serum creatinine depending on age: 2-5 years male and female: <=0.50 mg/dL 6-10 years male and female: <=0.59 mg/dL 11-15 years male and female: <=1.2 mg/dL >15 years male and female: <=1.5 mg/dL Metabolic (lipids): -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 The following specific criteria will be used to assign participants to Cohorts: Cohort 1 (Proteus syndrome with plantar CCTN) specific criteria: -Have at least one plantar CCTN that can accurately be measured by standardized photography. The CCTN is defined as a nevus with at least two gyri and three sulci affecting 10% - 70% of the total surface area of the foot. -Male or female participants age greater than or equal to 3 and less than or equal to 16 years old and BSA of greater than or equal to 0.33 m^2 Cohort 2 (Proteus syndrome without plantar CCTN) specific criteria: -Does not meet the eligibility criteria for Cohorts 1 or 3 -Male or female participants age greater than or equal to 3 years old and BSA of greater than or equal to 0.33 m^2 Cohort 3 (Proteus syndrome previously treated with miransertib) specific criteria: -Participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access or an existing trial (i.e., 16-HG-0014) -Male or female participants greater than or equal to 3 years old BSA of greater than or equal to 0.33 m^2 Note: All participants must meet Cohort-related age criteria by/on the date of the first dose, Cycle 1 Day 1 EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: - History of Type 1 or Type 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose greater than or equal to 160 mg/dL ( if >12 years old) and greater than or equal to 180 mg/dL (if less than or equal to 12 years old) at the baseline/screening visit -History of significant cardiac disorders: --Myocardial infarction (MI) or congestive heart failure defined as Class II-IV per the New York Heart Association (NYHA) classification within six months of the first dose of miransertib (MI occurring >6 months of the first dose of miransertib will be permitted) --Grade 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE v 5.0]) or worse conduction defect (e.g., right or left bundle branch block). -Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib -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 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
All participants in all Cohorts must meet the criteria below:
-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.
-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:
Hematological:
-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
Hepatic:
a. Total bilirubin <=2 x upper limit of normal (ULN)
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 x ULN
Renal:
a. Serum creatinine depending on age:
2-5 years male and female: <=0.50 mg/dL
6-10 years male and female: <=0.59 mg/dL
11-15 years male and female: <=1.2 mg/dL
>15 years male and female: <=1.5 mg/dL
Metabolic (lipids):
-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
The following specific criteria will be used to assign participants to Cohorts:
Cohort 1 (Proteus syndrome with plantar CCTN) specific criteria:
-Have at least one plantar CCTN that can accurately be measured by standardized photography. The CCTN is defined as a nevus with at least two gyri and three sulci affecting 10% - 70% of the total surface area of the foot.
-Male or female participants age greater than or equal to 3 and less than or equal to 16 years old and BSA of greater than or equal to 0.33 m^2
Cohort 2 (Proteus syndrome without plantar CCTN) specific criteria:
-Does not meet the eligibility criteria for Cohorts 1 or 3
-Male or female participants age greater than or equal to 3 years old and BSA of greater than or equal to 0.33 m^2
Cohort 3 (Proteus syndrome previously treated with miransertib) specific criteria:
-Participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access or an existing trial (i.e., 16-HG-0014)
-Male or female participants greater than or equal to 3 years old BSA of greater than or equal to 0.33 m^2
Note: All participants must meet Cohort-related age criteria by/on the date of the first dose, Cycle 1 Day 1
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
- History of Type 1 or Type 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose greater than or equal to 160 mg/dL ( if >12 years old) and greater than or equal to 180 mg/dL (if less than or equal to 12 years old) at the baseline/screening visit
-History of significant cardiac disorders:
--Myocardial infarction (MI) or congestive heart failure defined as Class II-IV per the New York Heart Association (NYHA) classification within six months of the first dose of miransertib (MI occurring >6 months of the first dose of miransertib will be permitted)
--Grade 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE v 5.0]) or worse conduction defect (e.g., right or left bundle branch block).
-Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib
-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 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
Principal Investigator
Referral Contact
For more information: