HemangiomaPhase 2NCT00555464
Clinical Trial of Vincristine vs. Prednisolone for Treatment of Complicated Hemangiomas
A Phase 2 study testing Vincristine and Prednisone in people with Hemangioma, run by Medical College of Wisconsin at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 6 months
- Conditions the study is for
- Hemangioma
- What is being tested?
- Vincristine and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Dec 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 6 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile
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.
Read the 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.
- Conditions
- Hemangioma
- Being tested
- Vincristine, Prednisone
- Keywords
- hemangioma, steroid, prednisolone, vincristine
- Medical subject headings
- Hemangioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VincristineDrug
Also called VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)
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.
PrednisoneDrug
Also called PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)
Prednisolone given at 3 mg/kg/day by mouth for 12 week
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (1)
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.
Measured: Initial visit, 2, 4, 6, 10 and 12 weeks of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: The introduction of oral propranolol as a highly efficacious agent for infantile hemangiomas
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HemangiomaStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Responsible party
- Principal investigator, Beth Drolet, Medical College of Wisconsin
- Investigators
- Beth Drolet, MD, Principal investigator, Medical College of WisconsinMichael Kelly, MD, PhD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00555464
- Sponsor's protocol ID
- 3429
- Other IDs
- #FDA-R-003429-01
- Status last verified
- Jun 2013
- First submitted
- 7 Nov 2007
- Last updated
- 11 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 8607636
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Clinical Trial Assessing Efficacy And Safety Of Oral Prednisolone vs Intravenous Vincristine In The Treatment Of Infantile
- ClinicalTrials.gov ID
- NCT00555464
- Acronym / sponsor ID
- 3429
- Conditions
- Hemangioma
- Keywords
- hemangioma, steroid, prednisolone, vincristine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The introduction of oral propranolol as a highly efficacious agent for infantile hemangiomas
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Collaborators
- FDA Office of Orphan Products Development
- Study start
- Nov 2007
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 8 Nov 2007 (estimated)
- Results
- Posted 11 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: VincristineVincristine 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 | Drug: PrednisoneThe 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. |
Who may qualify
- Ages
- Up to 6 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VincristineAlso: VINCRISTINE SULFATE (Oncovin®, VCR, LCR) NSC #67574 (042006)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. | Drug | 1 |
| PrednisoneAlso: PREDNISOLONE SODIUM PHOSPHATE SYRUP/SOLUTION 15mg/5 cc (Orapred®)Prednisolone given at 3 mg/kg/day by mouth for 12 week | Drug | 2 |
Primary outcome
Response of Hemangioma (IH) to Treatment
Time frame: 6 weeks
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.
1 secondary outcome
Toxicity to Medications
Time frame: Initial visit, 2, 4, 6, 10 and 12 weeks of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8607636Frieden 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.
- Children's Hospital of Wisconsin websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Beth Drolet, MD principal investigator
Medical College of Wisconsin
Michael Kelly, MD, PhD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vincristine and Prednisone in people with Hemangioma, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response of Hemangioma (IH) to Treatment (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00555464, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2013.