Study of Sirolimus Therapy for Segmental Overgrowth Caused by Somatic PI3K Activation

Inclusion Criteria

• •Age: greater than or equal to 3 years to less than or equal to 65 years
• •Male or Female
• •Confirmed PIK3CA somatic mutation
• •Measurably progressive overgrowth, in current progression or with clinical history of overgrowth progression
• •Adequate Bone Marrow Function Defined as:
• •* Peripheral absolute neutrophil count (ANC) greater than or equal to 1500/microliter, except for those participants with an absolute neutrophil count (ANC) of 1000-1500, caused by a benign condition associated with moderately decreased neutrophils known as Benign Ethnic Neutropenia (BEN), d those who have an ANC of 1000-1500 caused by a confirmed infection, which resolves with treatment of infection to greater than or equal to 1500.
• •* Platelet count less than or equal to 100,000/microliter
• •* Hemoglobin less than or equal to 10.0 gm/dL
• •Adequate Renal Function Defined as:
• •A serum creatinine based on age as follows:
• •* Age (years) \[Maximum Serum Creatinine (mg/dl)\]
• •* Less than or equal to 5 \[0.8 mg/dl\]
• •* 5 less than age less than or equal to10 \[1.0 mg/dl\]
• •* 10 less than age less than or equal to 15 \[1.2 mg/dl\]
• •* Less than 15 \[1.5 mg/dl\]
• •OR a creatinine clearance or radioisotope GFR greater than or equal to 70ml/min/1.73 m2
• •* Adequate Liver Function Defined As:
• •* Bilirubin (sum of conjugated + unconjugated) less than or equal to 1.5 x upper limit of normal (ULN) for age, and
• •* SGPT (ALT) less than or equal to 5 x upper limit of normal (ULN) for age, and
• •* Serum albumin greater than or equal to 2 g/dL.
• •* Fasting LDL Cholesterol:
• •* Patients must have a fasting LDL cholesterol of less than or equal to 160 mg/d
• •* All women of childbearing potential and all sexually active male patients must agree to use effective contraception
• •* Adolescent (15-17 year old) participants who are fluent in English and can thereby complete the pediatric self-report questionnaires and communicate well with the study team but whose parent(s) and/or legal guardian are primarily Spanish-speaking.