Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas - Full Text View

Sponsors and Collaborators:	FDA Office of Orphan Products Development Medical College of Wisconsin University of California, San Francisco Indiana University
Information provided by:	FDA Office of Orphan Products Development
ClinicalTrials.gov Identifier:	NCT00555464

Purpose

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.

Condition	Intervention	Phase
Hemangioma	Drug: Vincristine Drug: Prednisone	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Uncontrolled, Crossover Assignment, Safety/Efficacy Study
Official Title:	A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile

Resource links provided by NLM:

Drug Information available for: Prednisolone Prednisolone acetate Prednisone Depo-medrol Vincristine Medrol veriderm Methylprednisolone Prednisolone sodium phosphate Prednisolone Sodium Succinate Vincristine sulfate Methylprednisolone Sodium Succinate Methylprednisolone hemisuccinate 6-Methylprednisolone

U.S. FDA Resources

Further study details as provided by FDA Office of Orphan Products Development:

Primary Outcome Measures:

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

Secondary Outcome Measures:

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

Estimated Enrollment:	50
Study Start Date:	November 2007
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.	Drug: 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.
2: Active Comparator 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.	Drug: Prednisone Prednisolone given at 3 mg/kg/day by mouth for 12 week

Arms

Assigned Interventions

1: Experimental

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.

Drug: 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.

2: Active Comparator

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.

Drug: Prednisone

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

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

Ages Eligible for Study:	up to 6 Months
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 (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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555464

Contacts

Contact: Beth Drolet, MD	414-266-1569	bdrolet@mcw.edu
Contact: Michael E. Kelly, MD, PhD	414-456-4170	mekelly@mcw.edu

Locations

United States, California
University of California, San Francisco	Not yet recruiting
San Francisco, California, United States, 94143
Principal Investigator: Ilona Frieden, MD
United States, Indiana
Indiana University/Riley Children's Hospital	Not yet recruiting
Indianapolis, Indiana, United States, 46202
Principal Investigator: Anita Haggstrom, MD
United States, Wisconsin
Medical College of Wisconsin/Children's Hospital of Wisconsin	Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Beth Drolet, MD 414-266-1569 bdrolet@mcw.edu
Contact: Michael E Kelly, MD, PhD 414-456-4170 mekelly@mcw.edu
Principal Investigator: Beth Drolet, MD
Principal Investigator: Michael E Kelly, MD, PhD
Sub-Investigator: Paula North, MD, PhD

Sponsors and Collaborators

FDA Office of Orphan Products Development

Medical College of Wisconsin

University of California, San Francisco

Indiana University

Investigators

Principal Investigator:	Beth Drolet, MD	Medical College of Wisconsin
Principal Investigator:	Michael Kelly, MD, PhD	Medical College of Wisconsin

More Information

Additional Information:

Children's Hospital of Wisconsin website This link exits the ClinicalTrials.gov site

Publications:

1.Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in Children. NEJM 1999;341:173-180. 2.Haggstrom AN, Drolet BA, Baselga E, Chamlin S, Esterly NB, Garzon M, Horii K, Lucky A, Metry DW, Mancini AJ, Nopper A, Frieden IJ. Prospective study of infantile hemangiomas, part II:clinical characteristics predicting complications and treatment. Pediatrics 2006;118: 882-887. 3.Haggstrom A, Drolet BA, Baselga E, Chamlin SL, Esterly NB, Garzon MC,. Prospective study of infantile hemangiomas, Part I: Demographic, prenatal and perinatal characteristics. J Pediatr 2007; 150(3):291-4. 4.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. Archives of Dermatology 1996 132(3):307-11.

Responsible Party:	Medical College of Wisconsin ( Beth A. Drolet, MD & Michael E. Kelly, MD, Ph.D. )
Study ID Numbers:	3429, #FDA-R-003429-01
Study First Received:	November 7, 2007
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00555464 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by FDA Office of Orphan Products Development:

hemangioma, steroid, prednisolone, vincristine

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Antineoplastic Agents, Hormonal
Methylprednisolone
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Methylprednisolone acetate
Vincristine
Prednisolone acetate
Antimitotic Agents

Neuroprotective Agents
Glucocorticoids
Hormones
Sodium phosphate
Tubulin Modulators
Prednisolone
Hemangioma
Peripheral Nervous System Agents
Antineoplastic Agents, Phytogenic
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Prednisolone acetate
Neuroprotective Agents
Hormones
Therapeutic Uses
Neoplasms, Vascular Tissue
Hemangioma
Methylprednisolone Hemisuccinate

Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Mitosis Modulators
Gastrointestinal Agents
Vincristine
Methylprednisolone acetate
Antimitotic Agents
Protective Agents
Glucocorticoids
Pharmacologic Actions
Neoplasms
Autonomic Agents
Tubulin Modulators
Prednisolone
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 02, 2009