A Phase 1/2 Study of ARQ 092 (Miransertib) in Subjects with PIK3CA-related Overgrowth Spectrum (PROS) and Proteus Syndrome (PS)

Phase 1

• Conditions: PIK3CA-related overgrowth spectrum (PROS) and Proteus syndrome (PS).; MedDRA version: 20.0Level: LLTClassification code 10018058Term: Gene genetic abnormalitySystem Organ Class: 100000004850; MedDRA version: 20.0Level: LLTClassification code 10069758Term: Somatic mutationSystem Organ Class: 100000004867; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2016-000558-37-GB
• Lead Sponsor: ArQule, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-21
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

Inclusion Criteria - Part B
1.Signed informed consent, and when applicable, signed assent
2.Cohort 1 (PROS) specific criteria
•Male or female subjects = 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
3.Cohort 2 (PS) specific criteria
•Male or female subjects = 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 CCTN and pre-CCTN lesion that can be measured by standardized photography.
4.Cohort 3 specific criteria
•Male or female subjects =2 years old with BSA of = 0.33 m2 and who fail to meet the eligibility criteria for Cohorts 1 or 2
5.Cohort 4 (PROS or PS) specific criteria
•Subjects previously treated with ARQ 092 or currently receiving ARQ 092 under Compassionate Use/Expanded Access
Note: Subjects should meet the age criterion by/on the date of the first dose, Cycle 1 Day 1.

All Cohorts:
6.Archival or fresh overgrowth tissue sample available to be shipped to Sponsor or designee
7.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
8.Adequate organ function as indicated by the following laboratory values:
Hematological
a.Hemoglobin (Hgb) depending on age:
2-5 years male and female: = 10.0 g/dL
6-9 years male and female: = 11.5 g/dL
10-17 years female: = 11.0 g/dL
10-17 years male: = 11.5 g/dL
=18 years male and female: = 10.0 g/dL
b.Glycated hemoglobin (HbA1c): = 8% (= 64 mmol/mol)
c.Absolute neutrophil count (ANC): = 1.5 x 10_9/L
d.Platelet count = 150 x 10_9/L
Hepatic
a.Total bilirubin = 1.5 x upper limit of normal (ULN)/L
b.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x ULN
Renal
a.Serum creatinine depending on age:
2-5 years male and female: maximum 0.80 mg/dL
6-10 years male and female: maximum 1.0 mg/dL
11-15 years male and female: maximum 1.2 mg/dL
> 15 years male and female: maximum 1.5 mg/dL
b.Estimated Glomerular Filtration Rate (eGFR): = 60 mL/min/1.73 m2
Metabolic (lipids)
a.Cholesterol: = 400 mg/dL (= 10.34 mmol/L)
b.Triglyceride: = 500 mg/dL (= 5.7 mmol/L)
9.Male or female subjects 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 ARQ 092
10.Ability to complete the study questionnaires by the subject or his/her caregiver

Are the trial subjects under 18? yes
Number of subjects for this age range: 60
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 5
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Exclusion Criteria – Part B
1.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
2.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 ARQ 092 (MI occurring > 6 months of the first dose of ARQ 092 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 ARQ 092
3.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 ARQ 092
4.Intolerance of or severe toxicity attributed to AKT inhibitors (e.g., ARQ 092, uprosertib, afuresertib, ipatasertib)
5.Concurrent severe uncontrolled illness not related to PROS or PS, e.g.,
•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
6.Pregnant or breastfeeding
7.Inability to comply with study evaluations or to follow drug administration guidelines

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified