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

NCT00555464 | Terminated Phase 2 Results DMC

• 2 other identifiers: 3429#FDA-R-003429-01
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemangioma

Keywords

hemangioma, steroid, prednisolone, vincristine

Outcome Measures

Primary Outcomes (1)

• 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.

  6 weeks

Secondary Outcomes (1)

• Toxicity to Medications

  Initial visit, 2, 4, 6, 10 and 12 weeks of therapy

Study Arms (2)

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

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

Interventions

Vincristine 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.

Also known as: VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)

1

Prednisone DRUG

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

Also known as: PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)

2

Eligibility Criteria

• Age: Up to 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

Medical College of Wisconsin/Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 8607636 BACKGROUND

Related Links

• Children's Hospital of Wisconsin website

MeSH Terms

Conditions

Hemangioma

Interventions

Vincristine; Prednisone; Solutions; Methylprednisolone

Condition Hierarchy (Ancestors)

Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pharmaceutical Preparations; Prednisolone; Pregnadienetriols

Limitations and Caveats

The limitations of this trial include early termination of enrollment leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Beth Drolet, MD
• Organization: Medical College of Wisconsin

sjoachim@mcw.edu

414-955-2817

Study Officials

• Beth Drolet, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

• Michael Kelly, MD, PhD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Dermatology

Study Record Dates

• First Submitted: November 7, 2007
• First Posted: November 8, 2007
• Study Start: November 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 11, 2013
• Results First Posted: June 11, 2013

Record last verified: 2013-06

Locations

US (1)