Study of patients with an increase in the size of certain parts of their body and circulatory abnormalities.

Phase 1

• Conditions: subjects (at least 6 years) suffering from diseases overgrowth and vascular anomalies with genetic alterations of the PI3K / AKT pathway.; MedDRA version: 20.0 Level: SOC Classification code 10010331 Term: Congenital, familial and genetic disorders System Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-01-03
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Each prospective subject must meet ALL of the following inclusion criteria in order to be eligible for this study:
1. Male or female subjects = 6 years old
2. Overgrowth diseases or vascular anomalies with documented and/or confirmed somatic genetic alterations of PIK3CA, AKT, or PTEN defined/assessed as:
? Measureable segmental overgrowth, currently experiencing growth, or with clinical history of overgrowth progression
? Vascular and/or lymphatic overgrowth diseases as determined by clinical (such as dermatological), imaging (e.g., bi-dimensional/volumetric MRI, CT, ultrasound), and histological/cytological criteria
3. Subjects with significant morbidity, poor quality of life, or with disease characterized by poor prognosis
4. No standard systemic therapeutic option available or no satisfactory response to prior experimental or local therapies
5. Signed informed consent and, when applicable, signed assent
6. Hemoglobin (Hgb) depending on age:
? 6-9 years male and female: = 11.5 g/dL
? 10-17 years female: = 12.0 g/dL
? 10-17 years male: = 12.5 g/dL
? > 17 years male and female: = 10.0 g/dL
7. Absolute neutrophil count (ANC): = 1.5 x 109/L
8. Platelet count = 150 x 109/L (for subjects with KHE or MLT, platelet count must be = 75 x 109/L)
9. Total bilirubin = 1.5 x upper limit of normal (ULN)/L
10. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x ULN
11. Serum creatinine depending on age:
? 6-10 years male and female: maximum 0.59 mg/dL
? 11-15 years male and female: maximum 1.2 mg/dL
? > 15 years male and female: maximum 1.5 mg/dL
12. If a female is of child-bearing potential, documentation of a negative pregnancy test is required prior to enrollment. Sexually active subjects (male and female) must use adequate contraceptive measures while on study and for up to 90 days after ending treatment
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

Potential subjects who meet ANY of the following exclusion criteria are not eligible for enrollment into this study:
1. 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) and = 180 mg/dL (if = 12 years) at the screening visit
2. Grade = 2 (per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE version 4.03]) hypercholesterolemia or hypertriglyceridemia or > 8% glycated Hgb (HbA1C)
3. Malabsorption syndrome
4. History of myocardial infarction (MI) or New York Heart Association (NYHA) Class II-IV congestive heart failure within 6 months of the administration of the first dose of ARQ 092 (MI occurring > 6 months of the first dose of ARQ 092 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
5. Major surgery, chemotherapy, radiotherapy, or immunotherapy within four weeks of the first dose of ARQ 092
6. No experimental systemic therapy for the purpose of treating PIK3CA Related Overgrowth Spectrum (PROS) (e.g., sirolimus, everolimus, high dose steroids) within two weeks of first dose of ARQ 092
7. Previous treatment with AKT inhibitors
8. Concurrent severe uncontrolled illness not related to overgrowth diseases
9. Ongoing or active known infection, including human immunodeficiency virus (HIV) infection or bleeding
10. Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
11. Pregnant or breastfeeding
12. Severe hypersensitivity reactions to mTOR inhibitors (e.g., sirolimus, everolimus)
13. Insufficient language proficiency of the subject (or legal guardian) to complete the informed consent and quality of life questionnaires
14. Inability to swallow oral medications

Study & Design

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