Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03094832
Other study ID # 7075-002
Secondary ID MOSAICARQ 092-10
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date May 16, 2017
Est. completion date April 11, 2022

Study information

Verified date April 2023
Source ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is an open label, Phase 1/2 study of oral miransertib (MK-7075) administered to participants at least 2 years of age with phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)-related Overgrowth Spectrum (PROS) and Proteus Syndrome (PS) (MOSAIC).


Description:

The study consists of two parts: Part A and Part B. Part A was closed to enrollment under Amendment 6. As of Amendment 7, the endpoints for Part A and Part B have been combined to assess the safety and tolerability of miransertib in participants with PROS and PS. Previous efficacy and pharmacokinetic (PK) objectives and endpoints have been removed. Amendment 7 will complete the final enrollment into the MOSAIC study and Compassionate Use/Expanded Access Program.


Recruitment information / eligibility

Status Terminated
Enrollment 50
Est. completion date April 11, 2022
Est. primary completion date April 11, 2022
Accepts healthy volunteers No
Gender All
Age group 2 Years and older
Eligibility 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 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


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Australia Hunter Genetics ( Site 0201) Waratah NSW New South Wales
Italy Universita di Catania ( Site 0088) Catania
Italy Fondazione Policlinico Universitario A. Gemelli ( Site 0052) Roma
Italy Ospedale Pediatrico Bambino Gesu ( Site 0087) Rome Roma
Spain Hospital Sant Joan ( Site 0601) Esplugues de Llobregat Barcelona
United States Children's Hospital of Atlanta ( Site 0107) Atlanta Georgia
United States Boston Children's Hospital ( Site 0089) Boston Massachusetts
United States Ann & Robert H. Lurie Children's Hospital of Chicago ( Site 0101) Chicago Illinois
United States Cincinnati Children's Hospital Medical Center ( Site 0102) Cincinnati Ohio
United States Texas Children's Hospital ( Site 0104) Houston Texas
United States Seattle Childrens Hospital ( Site 0103) Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) Worldwide Clinical Trials

Countries where clinical trial is conducted

United States,  Australia,  Italy,  Spain, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Who Experienced an Adverse Event (AE) An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Up to approximately 48 months
Primary Number of Participants Who Discontinued Study Treatment Due to an AE An AE was defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product and does not imply any judgment about causality. Up to approximately 45 months