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

Primary Purpose

Hemangioma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Vincristine
Prednisone
Sponsored by
Medical College of Wisconsin
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemangioma focused on measuring hemangioma, steroid, prednisolone, vincristine

Eligibility Criteria

undefined - 6 Months (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Medical College of Wisconsin/Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Response of Hemangioma (IH) to Treatment
Response of IH not confined to the dermis will be coded using the following criteria: Progressive disease: >40% increase in volume by MRI, Partial response: >65% reduction in volume by MRI, Complete response: no visual or radiographic evidence of disease, Stable disease: none of the above or <40% increase or <65% decrease in volume by MRI. Response of superficial IH will be coded using the following criteria (based on RECIST): Progressive disease: >30% increase in IH size, Partial response: >30% reduction in size, Complete response: no evidence of disease, Stable disease: none of the above. Our first 3 patients showed limits to using MRI volume to measure IH size/response to therapy. Unlike other solid tumors, the superficial distribution of some IH made getting volume by MRI difficult, resulting in smaller tumor estimation compared to clinical assessment. Based on these observations, we amended the protocol to report response based on RECIST criteria instead of change in IH volume.

Secondary Outcome Measures

Toxicity to Medications
Adverse events were closely monitored and recorded at weekly visits during treatment period and for two years after treatment ceased. Laboratory values were taken every other week during the treatment period. Please see Adverse Events module for more details.

Full Information

First Posted
November 7, 2007
Last Updated
June 4, 2013
Sponsor
Medical College of Wisconsin
Collaborators
FDA Office of Orphan Products Development
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1. Study Identification

Unique Protocol Identification Number
NCT00555464
Brief Title
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

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Why Stopped
The introduction of oral propranolol as a highly efficacious agent for infantile hemangiomas
Study Start Date
November 2007 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical College of Wisconsin
Collaborators
FDA Office of Orphan Products Development

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemangioma
Keywords
hemangioma, steroid, prednisolone, vincristine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
8 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
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.
Arm Title
2
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)
Intervention Description
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
Intervention Name(s)
Prednisone
Other Intervention Name(s)
PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)
Intervention Description
Prednisolone given at 3 mg/kg/day by mouth for 12 week
Primary Outcome Measure Information:
Title
Response of Hemangioma (IH) to Treatment
Description
Response of IH not confined to the dermis will be coded using the following criteria: Progressive disease: >40% increase in volume by MRI, Partial response: >65% reduction in volume by MRI, Complete response: no visual or radiographic evidence of disease, Stable disease: none of the above or <40% increase or <65% decrease in volume by MRI. Response of superficial IH will be coded using the following criteria (based on RECIST): Progressive disease: >30% increase in IH size, Partial response: >30% reduction in size, Complete response: no evidence of disease, Stable disease: none of the above. Our first 3 patients showed limits to using MRI volume to measure IH size/response to therapy. Unlike other solid tumors, the superficial distribution of some IH made getting volume by MRI difficult, resulting in smaller tumor estimation compared to clinical assessment. Based on these observations, we amended the protocol to report response based on RECIST criteria instead of change in IH volume.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Toxicity to Medications
Description
Adverse events were closely monitored and recorded at weekly visits during treatment period and for two years after treatment ceased. Laboratory values were taken every other week during the treatment period. Please see Adverse Events module for more details.
Time Frame
Initial visit, 2, 4, 6, 10 and 12 weeks of therapy

10. Eligibility

Sex
All
Maximum Age & Unit of Time
6 Months
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beth Drolet, MD
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Michael Kelly, MD, PhD
Organizational Affiliation
Medical College of Wisconsin
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical College of Wisconsin/Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8607636
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.
Results Reference
background
Links:
URL
http://www.chw.org/display/PPF/DocID/36150/router.asp
Description
Children's Hospital of Wisconsin website

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

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