Clinical trial NCT00555464: Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas
Official title: A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hemangioma
Keywords: hemangioma, steroid, prednisolone, vincristine
Lead sponsor: Medical College of Wisconsin
Sponsor class: OTHER
Collaborators: name: FDA Office of Orphan Products Development
First posted: 2007-11-08
Enrollment: 8
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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(serum glutamate pyruvate transaminase) (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 (CNS) 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.

Primary outcomes:
measure: Response of Hemangioma (IH) to Treatment
timeFrame: 6 weeks
Secondary outcomes:
measure: Toxicity to Medications
timeFrame: Initial visit, 2, 4, 6, 10 and 12 weeks of therapy
Other outcomes:
Locations:
city: Milwaukee
country: United States
facility: Medical College of Wisconsin/Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Medical College of Wisconsin
name: Beth Drolet, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Michael Kelly, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frieden IJ, Reese V, Cohen D. PHACE syndrome. The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Arch Dermatol. 1996 Mar;132(3):307-11. doi: 10.1001/archderm.132.3.307.