Vascular AnomalyPhase 1NOVANCT04172922
Topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and Other Susceptible Lesions
A Phase 1 study testing Topical Sirolimus in people with Vascular Anomaly, run by Nemours Children's Clinic at 2 sites in United States.
Trial summary
Proposed Study: Treatment protocol for the use of the topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and other susceptible lesions 1. Aim The aim of this treatment study is to evaluate the benefit and tolerability of topical sirolimus applied to cutaneous vascular anomalies in pediatric patients. Read more about this study
- Who is it for?
- Ages 36 months to 21 years
- Conditions the study is for
- Vascular Anomaly
- What is being tested?
- Topical Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Apr 2020to 15 Feb 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 36 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients will be more than 36 months and less than 21 years of age.
- Newly diagnosed with vascular anomalies (VA) or have a VA that failed therapy with systemic sirolimus or other systemic or surgical therapies.
- Patients who have undergone surgical resection or interventional radiology procedures for disease control are eligible to start topical sirolimus
- At least 2 weeks since undergoing any major surgery.
- Must not have received Myelosuppressive chemotherapy within 4 weeks of starting sirolimus.
- At least 7 days since the completion of therapy with a GF that supports platelet, red or white cell number or function.
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- At least 14 days since the completion of therapy with a biologic agent.
- Patients with Kaposiform Hemagioendothelioma who have failed or are intolerant of systemic sirolimus therapy.
- Patients must not have received any non-FDA approved drug within 4 weeks or 5 half-lives, whichever is longer, prior to starting sirolimus and during treatment with sirolimus.
- XRT: > or = 6 months from involved field radiation to vascular tumor.
- Patients may not be currently receiving strong inhibitors of CYP3A4 and may not have received medications within 1 week of starting sirolimus.
- Patients may not be taking enzyme-inducing anticonvulsants, and may not have received these medications within 1 week of starting topical sirolimus, as these patients may experience different drug disposition.
- Adequate organ function
- Total bilirubin ≤1.5 x ULN for age
- SGPT (ALT) <5 x ULN for age
- Serum albumin > or = 2 g/dL.
- Fasting LDL cholesterol of <160 mg/dL
- Adequate Bone Marrow Function
- Hemoglobin > or = 8.0 gm/dL (may receive RBC transfusions)
- Platelet count > or = 50,000/microL (transfusion independent defined as not receiving a platelet transfusion within a 7 day period prior to sirolimus use)
- Adequate Renal Function
- A serum creatinine based on age
- Urine protein to creatinine ratio (UPC) < 0.3 g/l
- Karnofsky > or = 50 (>/=16 years of age) and Lansky >/ = 50 for patients < 16 years of age
Who cannot join
- Concurrent severe and/or uncontrolled medical disease which could compromise compliance with safety monitoring requirements for sirolimus (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
- Chronic treatment with systemic steroids or another immunosuppressive agent.
- Patients who require medications that inhibit/induce CYP3A4 enzyme activity to control concurrent medical conditions.
- Known history of HIV seropositivity or known immunodeficiency.
- Women who are pregnant or breast feeding.
- Males or females of reproductive potential should agree to use an effective contraceptive method during the period they are receiving topical sirolimus and for 3 months thereafter.
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- Patients unwilling or unable to comply with the safety monitoring requirements for sirolimus.
- Patients who currently have an uncontrolled infection, defined as receiving intravenous antibiotics.
- Patients with hemangioma
- Patients with symptomatic complicated vascular anomalies with severe systemic symptoms that will need systemic therapy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Nemours Children's Health, Jacksonville
Jacksonville, Florida, 32207
Nemours Children's Hospital, Florida
Orlando, Florida, 32827
About this study
Official title: Treatment Protocol for the Use of the Topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and Other Susceptible Lesions
Proposed Study: Treatment protocol for the use of the topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and other susceptible lesions
- Aim The aim of this treatment study is to evaluate the benefit and tolerability of topical sirolimus applied to cutaneous vascular anomalies in pediatric patients. The primary end point will be individually determined based on improvement in lesional clinical characteristics over baseline
- Rationale for topical sirolimus use in VA The rationale for the use of topical sirolimus is to minimize these potential side effects and risks. Data for the use of topical sirolimus for vascular anomalies at this time are anecdotal and case reports only. As such, this prospective protocol seeks to determine the effectiveness and tolerability of topical sirolimus on patients with vascular anomalies that have a cutaneous component.
- Experimental design This is an open-labeled efficacy trial with the aim to determine if topical sirolimus can be safe and efficacious in treating the cutaneous component of complicated vascular anomalies. Patients who meet eligibility criteria with a diagnosis of vascular anomaly (VA) with cutaneous component will be offered treatment with the investigational topical sirolimus. Patients will receive topical sirolimus therapy for a total of six months and will be monitored regularly at the research site for clinical response. Response will be based on pre-determined clinical criteria. Patients will be removed from study if there is no response at three months after initiation of therapy. Clinical response will be defined as improvement in measurable parameters defined at the time of initiation of therapy. These include
- Size of lesions, measured in two parallel longest diameters
- Flattening of lesion
- Number of vesicles
- Episodes of superinfection or bleeding
- Improvement in pain
- Drug Information The topical sirolimus formulation will be made at a concentration of 1% sirolimus ointment. Bulk sirolimus powder will be compounded in a liposomal base in a GMP level pharmaceutical company. This base will enhance drug penetration into the skin. It ensures adequate adhesion to the application area and a low degree of systemic absorption. Due to limited absorption only mild side effects are expected.
Read the detailed description
Patients with vascular anomalies (VA) have a spectrum of diseases that can be broadly classified into vascular tumors and malformations. Complicated vascular anomalies can cause disfigurement, chronic pain, and organ dysfunction with significant morbidity and mortality. Despite the severity of potential complications, we lack uniform guidelines for the treatment and response to treatment of children and young adults with these diseases. Pre-clinical and clinical data supporting the essential regulatory function of the PI3K/Akt/mTOR pathway in vascular growth and organization, and suggest a therapeutic target for patients with complicated vascular anomalies. Nemours Children's Hospital (NCH) and other groups have been successfully using the mTOR inhibitor siroli-mus in a selected group of patients with VA. NCH exclusively uses the systemic oral formulation of sirolimus. The potential toxicities of systemic sirolimus is well documented, and many patients do not tolerate systemic sirolimus. We hypothesize this study will advance our treatment options of vascular anomalies by offering topical sirolimus. This prospective open labeled study will allow us to determine the efficacy and tolerability of topical sirolimus in the treatment of complicated vascular anomalies. This will potentially generate data for the use of topical sirolimus as an alternative to systemic sirolimus for patients with complicated VA with a cutaneous component.
- Conditions
- Vascular Anomaly
- Being tested
- Topical Sirolimus
- Medical subject headings
- Vascular Malformations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical SirolimusDrug
Also called rapamycin
Open label, topical sirolimus (1%) cream will be applied to cutaneous component of complicated vascular anomalies twice daily for 4 weeks and once daily thereafter- for the duration of study.
| Study group | Role | What they receive |
|---|---|---|
| Open label, topical sirolimus arm | Experimental | Single arm, open label study of1% sirolimus ointment applied to affected area twice daily for the first four weeks followed by once daily for 5 months. Receives: Drug: Topical Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in Pain or local irritation
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Measured: 24 weeks
Cyst formation
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Measured: 24 weeks
Decrease in discharge
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Measured: 24 weeks
Decrease in cyst formation
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Measured: 24 weeks
Secondary outcomes (9)
Sirolimus level
Sirolimus level in ng/ml.
Measured: 24 weeks
Bilirubin level
Total bilirubin in mg/dL
Measured: 24 weeks
Neutrophil level
Neutrophil count in mm3
Measured: 24 weeks
ALT level
ALT level in units/liter
Measured: 24 weeks
Serum Albumin
Serum Albumin level in g/liter
Measured: 32 weeks
Fasting LDL
Fasting LDL level in mg/dl
Measured: 24 weeks
Hemoglobin level
Hemoglobin level in g/dl
Measured: 24 weeks
Platelet count
Platelet count in microliter
Measured: 24 weeks
Urine Protein/creatinine
Urine Protein/creatinine levels in mL/min
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start1 Apr 2020
- Primary completion15 Feb 2024
- Study completion15 Feb 2024
Why it stopped: IRB suspended and subsequent early termination
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular AnomalyStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig Johnson, Nemours Children's Clinic
- Investigators
- Craig Johnson, DO, Principal investigator, Nemours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04172922
- Sponsor's protocol ID
- NOVA0118
- Acronym
- NOVA
- Status last verified
- Dec 2025
- First submitted
- 8 Nov 2019
- Last updated
- 31 Dec 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Protocol for the Use of the Topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and Other Susceptible Lesions
- ClinicalTrials.gov ID
- NCT04172922
- Acronym / sponsor ID
- NOVA / NOVA0118
- Conditions
- Vascular Anomaly
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IRB suspended and subsequent early termination
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Study start
- 1 Apr 2020 (actual)
- Primary completion
- 15 Feb 2024 (actual)
- Study completion
- 15 Feb 2024 (actual)
- First posted
- 21 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Proposed Study: Treatment protocol for the use of the topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and other susceptible lesions
- Aim The aim of this treatment study is to evaluate the benefit and tolerability of topical sirolimus applied to cutaneous vascular anomalies in pediatric patients. The primary end point will be individually determined based on improvement in lesional clinical characteristics over baseline
- Rationale for topical sirolimus use in VA The rationale for the use of topical sirolimus is to minimize these potential side effects and risks. Data for the use of topical sirolimus for vascular anomalies at this time are anecdotal and case reports only. As such, this prospective protocol seeks to determine the effectiveness and tolerability of topical sirolimus on patients with vascular anomalies that have a cutaneous component.
- Experimental design This is an open-labeled efficacy trial with the aim to determine if topical sirolimus can be safe and efficacious in treating the cutaneous component of complicated vascular anomalies. Patients who meet eligibility criteria with a diagnosis of vascular anomaly (VA) with cutaneous component will be offered treatment with the investigational topical sirolimus. Patients will receive topical sirolimus therapy for a total of six months and will be monitored regularly at the research site for clinical response. Response will be based on pre-determined clinical criteria. Patients will be removed from study if there is no response at three months after initiation of therapy. Clinical response will be defined as improvement in measurable parameters defined at the time of initiation of therapy. These include
- Size of lesions, measured in two parallel longest diameters
- Flattening of lesion
- Number of vesicles
- Episodes of superinfection or bleeding
- Improvement in pain
- Drug Information The topical sirolimus formulation will be made at a concentration of 1% sirolimus ointment. Bulk sirolimus powder will be compounded in a liposomal base in a GMP level pharmaceutical company. This base will enhance drug penetration into the skin. It ensures adequate adhesion to the application area and a low degree of systemic absorption. Due to limited absorption only mild side effects are expected.
Detailed description
Patients with vascular anomalies (VA) have a spectrum of diseases that can be broadly classified into vascular tumors and malformations. Complicated vascular anomalies can cause disfigurement, chronic pain, and organ dysfunction with significant morbidity and mortality. Despite the severity of potential complications, we lack uniform guidelines for the treatment and response to treatment of children and young adults with these diseases. Pre-clinical and clinical data supporting the essential regulatory function of the PI3K/Akt/mTOR pathway in vascular growth and organization, and suggest a therapeutic target for patients with complicated vascular anomalies. Nemours Children's Hospital (NCH) and other groups have been successfully using the mTOR inhibitor siroli-mus in a selected group of patients with VA. NCH exclusively uses the systemic oral formulation of sirolimus. The potential toxicities of systemic sirolimus is well documented, and many patients do not tolerate systemic sirolimus. We hypothesize this study will advance our treatment options of vascular anomalies by offering topical sirolimus. This prospective open labeled study will allow us to determine the efficacy and tolerability of topical sirolimus in the treatment of complicated vascular anomalies. This will potentially generate data for the use of topical sirolimus as an alternative to systemic sirolimus for patients with complicated VA with a cutaneous component.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label, topical sirolimus arm | Experimental | Drug: Topical SirolimusSingle arm, open label study of1% sirolimus ointment applied to affected area twice daily for the first four weeks followed by once daily for 5 months. |
Who may qualify
- Ages
- 36 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Patients will be more than 36 months and less than 21 years of age.
- Newly diagnosed with vascular anomalies (VA) or have a VA that failed therapy with systemic sirolimus or other systemic or surgical therapies.
- Patients who have undergone surgical resection or interventional radiology procedures for disease control are eligible to start topical sirolimus
- At least 2 weeks since undergoing any major surgery.
- Must not have received Myelosuppressive chemotherapy within 4 weeks of starting sirolimus.
Key exclusion criteria (10 listed)
- Concurrent severe and/or uncontrolled medical disease which could compromise compliance with safety monitoring requirements for sirolimus (e.g. uncontrolled diabetes, uncontrolled hypertension, severe infection, severe malnutrition, chronic liver or renal disease, active upper GI tract ulceration).
- Chronic treatment with systemic steroids or another immunosuppressive agent.
- Patients who require medications that inhibit/induce CYP3A4 enzyme activity to control concurrent medical conditions.
- Known history of HIV seropositivity or known immunodeficiency.
- Women who are pregnant or breast feeding.
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 |
|---|---|---|
| Topical SirolimusAlso: rapamycinOpen label, topical sirolimus (1%) cream will be applied to cutaneous component of complicated vascular anomalies twice daily for 4 weeks and once daily thereafter- for the duration of study. | Drug | Open label, topical sirolimus arm |
Primary outcome
Reduction in Pain or local irritation
Time frame: 24 weeks
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Cyst formation
Time frame: 24 weeks
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Decrease in discharge
Time frame: 24 weeks
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
Decrease in cyst formation
Time frame: 24 weeks
Response will be evaluated by physical exam and documented at 24 weeks of therapy.
9 secondary outcomes
Sirolimus level
Time frame: 24 weeks
Bilirubin level
Time frame: 24 weeks
Neutrophil level
Time frame: 24 weeks
ALT level
Time frame: 24 weeks
Serum Albumin
Time frame: 32 weeks
Fasting LDL
Time frame: 24 weeks
Hemoglobin level
Time frame: 24 weeks
Platelet count
Time frame: 24 weeks
Urine Protein/creatinine
Time frame: 24 weeks
Results and safety
The study was stopped early (reason given: IRB suspended and subsequent early termination). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Dec 2025.
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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.
Craig Johnson, DO principal investigator
Nemours
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Topical Sirolimus in people with Vascular Anomaly, run by Nemours Children's Clinic at 2 sites 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 24 inclusion and 10 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 31 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: IRB suspended and subsequent early termination). Results are not available in the source record.
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?
Reduction in Pain or local irritation (time frame: 24 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Dec 2025.