Study of ARQ 092 in Patients With Overgrowth Diseases and Vascular Anomalies

Description

This is an open label, Phase 1/2 study of oral ARQ 092 administered to patients at least 6 years of age with overgrowth diseases and vascular anomalies with genetic alterations of the PI3K/AKT pathway.

Study Start Date

May, 30 2017

Estimated Completion Date

June 2020

Interventions

  • Drug: ARQ 092

Study ID

ArQule -- ARQ 092-103

Status

Recruiting

Trial ID

NCT03094832

Study Type

Interventional

Trial Phase

Phase 1/Phase 2

Enrollment Quota

16

Sponsor

ArQule

Inclusion Criteria 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 Kaposiform Hemangioendotheliomas (KHE) or Multifocal Lymphangio-endotheliomatosis with Thrombocytopenia (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 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.

    Exclusion Criteria

      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 NCI CTCAE version 4.03 or worse 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 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. Any experimental systemic therapy for the purpose of treating PROS (e.g., sirolimus, everolimus, high dose steroids) within two weeks of the 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 mammilian target of rapamycin (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
  • Gender

    All

    Ages

    6 Years and older

    Accepts Healthy Volunteers

    No

    Study Locations and Contact Information (4)

    Study Location Distance Name Phone Email
    Boston Childrens Hospital - Boston, Massachusetts 2.6 miles ArQule 781-994-0300 ClinicalTrials@arqule.com
    Boston Childrens Hospital - Boston, Massachusetts 2.6 miles ArQule 781-994-0300 ClinicalTrials@arqule.com
    Boston Childrens Hospital - Boston, Massachusetts 2.6 miles ArQule 781-994-0300 ClinicalTrials@arqule.com
    Boston Childrens Hospital - Boston, Massachusetts 2.6 miles ArQule 781-994-0300 ClinicalTrials@arqule.com

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