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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03094832




Registration number
NCT03094832
Ethics application status
Date submitted
17/03/2017
Date registered
29/03/2017

Titles & IDs
Public title
Study of Miransertib (MK-7075) in Participants With PIK3CA-related Overgrowth Spectrum and Proteus Syndrome (MOSAIC) (MK-7075-002)
Scientific title
A Phase 1/2 Study of ARQ 092 (Miransertib) in Subjects With PIK3CA-related Overgrowth Spectrum and Proteus Syndrome
Secondary ID [1] 0 0
MOSAIC
Secondary ID [2] 0 0
7075-002
Universal Trial Number (UTN)
Trial acronym
MOSAIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PIK3CA-Related Overgrowth Spectrum (PROS)/Proteus Syndrome 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Miransertib

Experimental: Part A: Miransertib PROS/PS - During Cycles 1-3, participants with either PROS (phosphatidylinositol- 4,5-bisphosphate 3-kinase, catalytic subunit alpha \[PIK3CA\]-related Overgrowth Spectrum) or PS (Proteus syndrome) received miransertib 15 mg/m\^2 once daily (QD) (each cycle length = 28 days). From Cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 and then titrated to 35 mg/m\^2 orally QD at the investigator's discretion.

Experimental: Part B: Miransertib PROS (Cohort 1) - During Cycles 1-3, participants with PROS who have a measurable lesion by volumetric magnetic resonance imaging (MRI) received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Experimental: Part B: Miransertib PS (Cohort 2) - During Cycles 1-3, participants with PS who have a measurable lesion by standardized digital photography received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Experimental: Part B: Miransertib PROS/PS (Cohort 3) - During Cycles 1-3, participants with PROS or PS who do not meet all the eligibility criteria for Cohorts 1 or 2 received miransertib 15 mg/m\^2 QD (each cycle length = 28 days). From cycles 4-48 or until disease progression, unacceptable toxicity, or discontinuation, participants received miransertib dose titrated to 25 mg/m\^2 orally QD at the investigator's discretion.

Experimental: Part B: Miransertib Compassionate Use/Expanded Access (Cohort 4) - During cycles 1-48 (each cycle length = 28 days) or until disease progression, unacceptable toxicity, or discontinuation, participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access continued to receive the current dose of miransertib (did not exceed 25 mg/m\^2).


Treatment: Drugs: Miransertib
Miransertib capsules administered orally at an initial dose of 15 mg/m\^2 or 25 mg/m\^2 QD and then titrated up to 25 mg/m\^2 or 35 mg/m\^2 QD at the investigator's discretion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [1] 0 0
Up to approximately 48 months
Primary outcome [2] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [2] 0 0
Up to approximately 45 months

Eligibility
Key inclusion criteria
Part A

* Signed informed consent and, when applicable, signed assent
* Male or female participants = 2 years old with body surface area (BSA) of = 0.33 m^2
* Have a clinical diagnosis of PROS or PS with documented somatic PIK3CA or serine-threonine protein kinase (AKT1) mutations
* Archival or fresh overgrowth tissue sample available to be shipped to Sponsor or designee
* Have poor prognosis, significant morbidity, and/or progressive disease (e.g., worsening of the disease/increase in number or size of the overgrowth lesions in the last 12 months)
* Have measurable disease (at least one overgrowth lesion that can be accurately measured in size by imaging and/or linear or circumference measure)
* Adequate organ function based on screening laboratory values
* 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 Quality of Life (QoL) questionnaires by the participant or his/her caregiver

Part B:

* Signed consent form and when applicable, signed assent
* Archival or fresh overgrowth tissue sample available to be shipped to Sponsor or designee
* Except for Cohort 4, clinically progressive or worsening disease defined as an increase in number or size of the overgrowth lesion(s) in the last 6 months as assessed by the Investigator
* Adequate organ function based on screening laboratory values
* Male or female participants of child-producing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after the last dose of miransertib
* Ability to complete the study questionnaires by the participant or his/her caregiver

Cohort 1 (PROS) specific criteria

* Male or female participants = 2 years and =30 years of age with BSA of = 0.33 m2
* Have clinical diagnosis of PROS per Diagnostic Criteria for PROS and documented somatic PIK3CA variant
* Have at least one lesion that can be measured by study- standardized volumetric MRI (eligibility to be confirmed by blinded independent central imaging review

- Cohort 2 (PS) specific criteria
* Male or female participants = 2 years and =18 years of age with BSA of = 0.33 m2
* Have clinical diagnosis of PS per Diagnostic Criteria for PS and documented somatic AKT1 variant
* Have at least one plantar cerebriform connective tissue nevus (CCTN) and pre-CCTN lesion that can be measured by standardized photography

* Cohort 3 specific criteria: Male or female participants =2 years old with BSA of = 0.33 m2 and who fail to meet the eligibility criteria for Cohorts 1 or 2
* Cohort 4 (PROS or PS) specific criteria: participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access. Participants should meet the age criterion by/on the date of the first dose, Cycle 1 Day 1
Minimum age
2 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

Part A:

* History of Type 1 or 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose = 160 mg/dL (if > 12 years old) and = 180 mg/dL (if = 12 years old) at the 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 6 months of the first dose of miransertib (MI occurring > 6 months of the first dose of miransertib will be permitted)
* Grade 2 (per NCI CTCAE version 4.03) or worse conduction defect (e.g., right or left bundle branch block); left ventricular ejection fraction (LVEF) < 50% assessed by echocardiogram/multigated acquisition (MUGA) scan
* Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib
* Any experimental systemic therapy for the purpose of treating PROS or PS (e.g., sirolimus, everolimus, high dose steroids) 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
* Intolerance of or severe toxicity attributed to v-Akt murine thymoma viral oncogene homolog (AKT) inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib)
* Concurrent severe uncontrolled illness not related to PROS or PS (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
* Inability to comply with study evaluations or to follow drug administration guidelines

Part B

* History of Type 1 diabetes mellitus or Type 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose = 160 mg/dL (if > 12 years old) and = 180 mg/dL (if = 12 years old) at the 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 6 months of the first dose of miransertib (MI occurring > 6 months of the first dose of miransertib will be permitted)
* Grade 2 (per current version of National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]) or worse conduction defect (e.g., right or left bundle branch block)
* Major surgery or locoregional therapy within four weeks of the first dose of miransertib
* Any experimental systemic therapy for the purposes of treating PROS or PS (e.g., sirolimus, everolimus, high dose steroids) within two weeks of the first dose of miransertib
* Intolerance of or severe toxicity attributed to AKT inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib)
* Concurrent severe uncontrolled illness not related to PROS or PS (e.g. ongoing or active infection, known HIV infection, malabsorption syndrome, psychiatric illness/substance abuse/social situation that would limit compliance with study requirements)
* Pregnant or breastfeeding
* Inability to comply with study evaluations or to follow drug administration guidelines

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/05/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/04/2022
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Hunter Genetics ( Site 0201) - Waratah NSW
Recruitment postcode(s) [1] 0 0
2298 - Waratah NSW
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
Italy
State/province [7] 0 0
Roma
Country [8] 0 0
Italy
State/province [8] 0 0
Catania
Country [9] 0 0
Spain
State/province [9] 0 0
Barcelona

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Worldwide Clinical Trials
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03094832