Topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and Other Susceptible Lesions (NOVA)

This is an interventional treatment trial for Vascular Anomaly Read More

Inclusion Criteria:

• Patients will be more than 36 months and less than 21 years of age.
• Newly diagnosed with vascular anomalies (VA) or have a VA that failed therapy with systemic sirolimus or other systemic or surgical therapies.
• Patients who have undergone surgical resection or interventional radiology procedures for disease control are eligible to start topical sirolimus
• At least 2 weeks since undergoing any major surgery.
• Must not have received Myelosuppressive chemotherapy within 4 weeks of starting sirolimus.
• At least 7 days since the completion of therapy with a GF that supports platelet, red or white cell number or function.
• At least 14 days since the completion of therapy with a biologic agent.
• Patients with Kaposiform Hemagioendothelioma who have failed or are intolerant of systemic sirolimus therapy.
• Patients must not have received any non-FDA approved drug within 4 weeks or 5 half-lives, whichever is longer, prior to starting sirolimus and during treatment with sirolimus.
• XRT: > or = 6 months from involved field radiation to vascular tumor.
• Patients may not be currently receiving strong inhibitors of CYP3A4 and may not have received medications within 1 week of starting sirolimus.
• Patients may not be taking enzyme-inducing anticonvulsants, and may not have received these medications within 1 week of starting topical sirolimus, as these patients may experience different drug disposition.
• Adequate organ function
• Total bilirubin ≤1.5 x ULN for age
• SGPT (ALT) <5 x ULN for age
• Serum albumin > or = 2 g/dL.
• Fasting LDL cholesterol of <160 mg/dL
• Adequate Bone Marrow Function
• Hemoglobin > or = 8.0 gm/dL (may receive RBC transfusions)
• Platelet count > or = 50,000/microL (transfusion independent defined as not receiving a platelet transfusion within a 7 day period prior to sirolimus use)
• Adequate Renal Function
• A serum creatinine based on age
• Urine protein to creatinine ratio (UPC) < 0.3 g/l
• Karnofsky > or = 50 (>/=16 years of age) and Lansky >/ = 50 for patients < 16 years of age

Exclusion Criteria:

• Concurrent severe and/or uncontrolled medical disease which could compromise compliance with safety monitoring requirements for sirolimus (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
• Chronic treatment with systemic steroids or another immunosuppressive agent.
• Patients who require medications that inhibit/induce CYP3A4 enzyme activity to control concurrent medical conditions.
• Known history of HIV seropositivity or known immunodeficiency.
• Women who are pregnant or breast feeding.
• Males or females of reproductive potential should agree to use an effective contraceptive method during the period they are receiving topical sirolimus and for 3 months thereafter.
• Patients unwilling or unable to comply with the safety monitoring requirements for sirolimus.
• Patients who currently have an uncontrolled infection, defined as receiving intravenous antibiotics.
• Patients with hemangioma
• Patients with symptomatic complicated vascular anomalies with severe systemic symptoms that will need systemic therapy.