Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas

NCT ID: NCT00555464

Last Updated: 2013-06-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2012-12-31

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.

Conditions

Hemangioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Vincristine

Intervention Type: DRUG

Vincristine (0.05 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.

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.

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

Prednisolone given at 3 mg/kg/day by mouth for 12 week

Interventions

Vincristine

Vincristine (0.05 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.

Intervention Type: DRUG

Prednisone

Prednisolone given at 3 mg/kg/day by mouth for 12 week

Intervention Type: DRUG

Other Intervention Names

VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006); PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)

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.
• 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.

• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: lead

Responsible Party

Beth Drolet

Professor of Dermatology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Beth Drolet, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Michael Kelly, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Locations

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 8607636 (View on PubMed)

Related Links

http://www.chw.org/display/PPF/DocID/36150/router.asp

Children's Hospital of Wisconsin website

Other Identifiers

#FDA-R-003429-01

Identifier Type: -

Identifier Source: secondary_id

3429

Identifier Type: -

Identifier Source: org_study_id