Official Title: “A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile”

The goal of this study is to determine the safety and efficacy of Prednisolone and Vincristine for treatment of large, complicated infantile hemangiomas. The diagnostic, therapeutic and response criteria experimentally determined in this study will be used as a framework for future infantile hemangioma studies.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study

Infants with large hemangiomas are often treated systemically with oral steroids (Prednisolone) to prevent complications. The best treatment for hemangiomas is not known and there are no medications approved by the FDA for treatment of hemangiomas. Also, the best method to measure the response of hemangioma to treatment is not known. Patients enrolling on this study will be randomly assigned to receive either daily Prednisolone by mouth or weekly Vincristine in a vein. Response to treatment will be monitored by clinical exams every two weeks and by an MRI at study entry and six and twelve weeks later. Patients with evidence of progressive disease (larger hemangiomas) on the week 6 MRI will be switched to the other drug to complete a total of 12 weeks of therapy. Side effects of each medication will be monitored closely determined from histories, physical exams, blood tests and other studies as necessary. Participation in this study will last up to 12 weeks and follow up for protocol.

Intervention(s) in this Clinical Trial

• Drug: Vincristine
  • Vincristine (0.5 mg/kg/dose) will be administered into a vein (PICC line) every week for 12 weeks. If assigned to receive Vincristine, a PICC line will be placed by a doctor who is a specialist in this procedure, an interventional radiologist. This will require sedation and when possible, will be coordinated with sedation for the MRI.
• Drug: Prednisone
  • Prednisolone given at 3 mg/kg/day by mouth for 12 week

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Vincristine is a drug that has been used to treat cancers in children (including infants). It has been effective in treating a small number of infants with hemangiomas, most of whom failed previous therapies including steroids. Vincristine must be administered into a vein. Given the encouraging response data and documented safety record, Vincristine is a good choice for a clinical trial treating infants with complicated hemangiomas.
• Active Comparator: 2
  • The standard treatment for hemangioma at most centers is oral steroids (Prednisolone). Prednisolone has been used to stop the growth of infantile hemangiomas that are life threatening, that could harm important functions, or are likely to result in severe disfigurement (scarring) without treatment.

Primary Measures

• Decrease in size of hemangioma by MRI and clinical exam
  • Time Frame: Initial visit, 6 weeks, 12 weeks
    

Secondary Measures

• Toxicity to medications
  • Time Frame: Initial visit, 2, 4, 6, 10 and 12 weeks of therapy
    

Inclusion Criteria:

• Children age 0-6 months old.
• Infants with infantile hemangiomas with complications that require systemic therapy to control their growth. To be eligible for enrollment infants must have clear indications for systemic treatment.
• Clinical diagnosis of infantile hemangioma confirmed by tissue biopsy positive for
• GLUT-1 Immunohistochemical staining. If the risk of bleeding or permanent disfigurement from biopsy is believed to be too great then clinical and radiological characteristics may be used to establish the diagnosis after discussion with the study
• PI. Patients with GLUT-1 negative vascular tumors such as Kaposiform hemangioendothelioma, tufted angioma, and angiosarcoma are not eligible.
• Hemangiomas must be greater than or equal to 50 cm2 clinically measured by taking the product of the two largest perpendicular diameters and have one of the following complications: ulceration, impairment of vision, impairment of hearing, obstruction of the airway, high output cardiac failure, bleeding, abdominal distention and/or compartment syndrome, compression of the spinal cord, or high risk of permanent disfigurement.
• Adequate liver function defined as:
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age.
• Patients who have received topical or intralesional corticosteroids are eligible to be enrolled. A washout of one week is required prior to study enrollment. Patients who have undergone surgical resection are eligible if they meet all

inclusion criteria

• after surgery.
• All patients' parents or legal guardians must sign a written informed consent. All institutional and FDA requirements for human studies must be met.

Exclusion Criteria:

• Children greater then 6 months old.
• Contraindications to Vincristine: previously diagnosed neuropathy including sensory neuropathy type 1, Charcot- Marie-Tooth or childhood poliomyelitis.
• Hemangioma involving the central nervous system as Vincristine has poor CNS penetration.
• Infants who have received prior systemic therapy with corticosteroids (oral or intravenous), interferon or Vincristine are not eligible for enrollment.
• Patients receiving Vincristine who concomitantly require oral steroids for treatment of non-hemangioma indications such as asthma or atopic dermatitis will be removed from study.
• A life-threatening intercurrent infection.
• Infants with an underlying illness that would require use of general anesthesia (as opposed to sedation) for the MRI.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: 6 Months

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: FDA Office of Orphan Products Development

Overall Clinical Trial Officials and Contacts

Beth Drolet, MD Principal Investigator Medical College of Wisconsin  

Overall Contact: Beth Drolet, MD 414-266-1569 bdrolet@mcw.edu

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00555464

Study ID Number: 3429

ClinicalTrials.gov Identifier: NCT00555464

Health Authority: United States: Food and Drug Administration

Children's Hospital of Wisconsin website