Topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and Other Susceptible Lesions

NCT04172922 | Terminated Phase 1 FDA Drug

• 1 other identifier: NOVA0118
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

Proposed Study: Treatment protocol for the use of the topical Rapamycin/Sirolimus for Complicated Vascular Anomalies and other susceptible lesions

1. 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. The primary end point will be individually determined based on improvement in lesional clinical characteristics over baseline
2. 2.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.
3. 3.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.
4. 4.Size of lesions, measured in two parallel longest diameters
5. 5.Flattening of lesion
6. 6.Number of vesicles
7. 7.Episodes of superinfection or bleeding
8. 8.Improvement in pain
9. 9.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.

Conditions

Vascular Anomaly

Outcome Measures

Primary Outcomes (4)

• Reduction in Pain or local irritation

  Response will be evaluated by physical exam and documented at 24 weeks of therapy.

  24 weeks

• Cyst formation

  Response will be evaluated by physical exam and documented at 24 weeks of therapy.

  24 weeks

• Decrease in discharge

  Response will be evaluated by physical exam and documented at 24 weeks of therapy.

  24 weeks

• Decrease in cyst formation

  Response will be evaluated by physical exam and documented at 24 weeks of therapy.

  24 weeks

Secondary Outcomes (9)

• Sirolimus level

  24 weeks

• Bilirubin level

  24 weeks

• Neutrophil level

  24 weeks

• ALT level

  24 weeks

• Serum Albumin

  32 weeks

Other Outcomes (7)

• Changes in vital signs

  24 weeks

• Temperature

  24 weeks

• Respirations

  24 weeks

Study Arms (1)

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.

Drug: Topical Sirolimus

Interventions

Topical Sirolimus DRUG

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.

Also known as: rapamycin

Open label, topical sirolimus arm

Eligibility Criteria

• Age: 36 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Nemours Children's Clinic: lead

Study Sites (2)

Nemours Children's Health, Jacksonville

Jacksonville, Florida, 32207, United States

Location

Nemours Children's Hospital, Florida

Orlando, Florida, 32827, United States

Location

MeSH Terms

Conditions

Vascular Malformations

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Craig Johnson, DO

  Nemours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Radiology Chair

Study Record Dates

• First Submitted: November 8, 2019
• First Posted: November 21, 2019
• Study Start: April 1, 2020
• Primary Completion: February 15, 2024
• Study Completion: February 15, 2024
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

US (2)