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

This study is currently recruiting participants.
Verified by FDA Office of Orphan Products Development, November 2007

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

ChemIDplus related topics:   Prednisolone    6-Methylprednisolone    Depo-medrol    Medrol veriderm    Methylprednisolone    Methylprednisolone hemisuccinate    Methylprednisolone Sodium Succinate    Prednisolone acetate    Prednisolone sodium phosphate    Prednisolone Sodium Succinate    Prednisone    Vincristine sulfate    Vincristine    Sodium phosphate, dibasic   

U.S. FDA Resources

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

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

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 (0.5 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.
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

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

Study ID Numbers:   3429, #FDA-R-003429-01
First Received:   November 7, 2007
Last Updated:   July 1, 2008
ClinicalTrials.gov Identifier:   NCT00555464
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:
Prednisone
Sodium phosphate
Methylprednisolone
Prednisolone
Hemangioma
Vincristine
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone Hemisuccinate

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Antimitotic Agents
Protective Agents
Neuroprotective Agents
Glucocorticoids
Hormones
Pharmacologic Actions
Neoplasms
Autonomic Agents
Therapeutic Uses
Tubulin Modulators
Neoplasms, Vascular Tissue
Peripheral Nervous System Agents
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 05, 2008




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