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

Sponsor:	Medical College of Wisconsin
Collaborator:	FDA Office of Orphan Products Development
Information provided by:	Medical College of Wisconsin
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:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
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:

MedlinePlus related topics: Birthmarks

Drug Information available for: Prednisolone Prednisolone acetate Prednisone Depo-medrol Vincristine Sodium phosphate, dibasic 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 Medical College of Wisconsin:

Primary Outcome Measures:

Decrease in size of hemangioma by MRI and clinical exam [ Time Frame: Initial visit, 6 weeks, 12 weeks ] [ Designated as safety issue: Yes ]
A data and Safety Monitoring Board will be reviewing the data from this research throughout the study. We will tell you about new information from this or other studies that may affect your child's health, welfare, or willingness to stay in the study.

Secondary Outcome Measures:

Toxicity to medications [ Time Frame: Initial visit, 2, 4, 6, 10 and 12 weeks of therapy ] [ Designated as safety issue: Yes ]
Your child will have blood draws and be seen regularily in the clinic. This study is also monitored by Data and Safety monitoring Board and you will be notified of new information affect safety of the study.

Enrollment:	8
Study Start Date:	November 2007
Estimated Study Completion Date:	January 2012
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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. Other Name: VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)
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.	Drug: Prednisone Prednisolone given at 3 mg/kg/day by mouth for 12 week Other Name: PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)

Arms

Assigned Interventions

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.

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.

Other Name: VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)

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.

Drug: Prednisone

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

Other Name: PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)

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

Locations

United States, Wisconsin
Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Medical College of Wisconsin

FDA Office of Orphan Products Development

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:	Beth A. Drolet, MD & Michael E. Kelly, MD, Ph.D., Medical College of Wisconsin
ClinicalTrials.gov Identifier:	NCT00555464 History of Changes
Other Study ID Numbers:	3429, #FDA-R-003429-01
Study First Received:	November 7, 2007
Last Updated:	July 6, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:

hemangioma, steroid, prednisolone, vincristine

Additional relevant MeSH terms:

Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisone
Prednisolone phosphate
Vincristine
Sodium phosphate
Anti-Inflammatory Agents
Therapeutic Uses

Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents
Tubulin Modulators

ClinicalTrials.gov processed this record on February 12, 2012