Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| #FDA-R-003429-01 |
Not provided
Not provided
Not provided
The introduction of oral propranolol as a highly efficacious agent for infantile hemangiomas
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| FDA Office of Orphan Products Development | FED |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Initial visit, 2, 4, 6, 10 and 12 weeks of therapy |
Not provided
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:
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:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Beth Drolet, MD | Medical College of Wisconsin | Principal Investigator |
| Michael Kelly, MD, PhD | Medical College of Wisconsin | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical College of Wisconsin/Children's Hospital of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8607636 | Background | 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. |
| Label | URL |
|---|---|
| Children's Hospital of Wisconsin website | View source |
Not provided
Subjects meeting eligibility criteria including diagnosis and lesional size criteria were enrolled in the study. Subjects who had received topical or intralesional corticosteroids were eligible following a 1 week wash-out period.
Study participants were recruited from the Pediatric Dermatology clinic at Children's Hospital of Wisconsin between. Study enrollment period extended from 2008-2009.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Vincristine Treatment Group | 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. 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. |
| FG001 | Oral Steroid Treatment Group | 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. Prednisone : Prednisolone given at 3 mg/kg/day by mouth for 12 week |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Vincristine Treatment Group | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Per protocol, all participants were analyzed, no matter the treatment arm or treatment success. | Posted | Number | participants | 6 weeks |
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vincristine Treatment Group | 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. 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. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal: weight loss | Gastrointestinal disorders |
The limitations of this trial include early termination of enrollment leading to small numbers of subjects analyzed.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Beth Drolet, MD | Medical College of Wisconsin | 414-955-2817 | sjoachim@mcw.edu |
Not provided
| ID | Term |
|---|---|
| D006391 | Hemangioma |
| ID | Term |
|---|---|
| D009383 | Neoplasms, Vascular Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| D014750 | Vincristine |
| D011241 | Prednisone |
| D012996 | Solutions |
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Prednisone | Drug | Prednisolone given at 3 mg/kg/day by mouth for 12 week |
|
|
| BG001 | Oral Steroid Treatment Group | 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. Prednisone : Prednisolone given at 3 mg/kg/day by mouth for 12 week |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Vincristine Treatment Group | 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. 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. |
| OG001 | Oral Steroid Treatment Group | 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. Prednisone : Prednisolone given at 3 mg/kg/day by mouth for 12 week |
|
|
| Secondary | 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. | Posted | Number | participants | Initial visit, 2, 4, 6, 10 and 12 weeks of therapy |
|
|
|
| 0 |
| 4 |
| 3 |
| 4 |
| EG001 | Oral Steroid Treatment Group | 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. Prednisone : Prednisolone given at 3 mg/kg/day by mouth for 12 week | 0 | 4 | 0 | 4 |
| Anemia | Blood and lymphatic system disorders |
|
| obstruction/stenosis of airway | Respiratory, thoracic and mediastinal disorders |
|
| Infection with normal ANC | Infections and infestations |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | MedDRA (6.1) |
|
Not provided
Not provided
| D006571 |
| Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011244 | Pregnadienediols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D004364 | Pharmaceutical Preparations |
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |