An Open-Label, Single-Arm Exploratory Clinical Study of Everolimus for the Treatment of Vascular Malformations

NCT07037238 | Recruiting Phase 2

• 1 other identifier: hongtao1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-arm exploratory trial conducted by Xuanwu Hospital, Capital Medical University, aiming to evaluate the efficacy and safety of everolimus monotherapy in adult patients with vascular malformations.

Conditions

Vascular Malformations

Keywords

Vascular malformations; mTOR Inhibitors; Pharmacological Treatment

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) assessed by MRI

  1 year

Secondary Outcomes (9)

• Duration of Response (DOR) and 1-year DOR rate assessed by MRI

  1 year

• Mean Percentage Reduction in Target Lesion Volume at 3, 6, and 12 Months Assessed by MRI

  1 year

• Changes in Perilesional Microbleeds and Iron Deposition at 3, 6, and 12 Months Assessed by MRI QSM Sequence.

  1 year

• Changes in lesion hemorrhage risk during the follow-up period

  1 year

• The frequency and severity of intracranial hemorrhage events during the follow-up period were assessed through clinical records, imaging examinations (MRI), and the mRS scoring system.

  1 year

Other Outcomes (5)

• Incidence of Treatment-Emergent Adverse Events

  1year

• Changes in patients' FACIT scores during the follow-up period

  1year

• Pharmacokinetic (PK) profile/parameters

  1 year

Study Arms (1)

An Open-Label, Single-Arm Exploratory Study of Everolimus

EXPERIMENTAL

Subjects will receive everolimus 10 mg orally once daily in continuous 28-day treatment cycles, until the occurrence of disease progression, intolerable toxicity, lack of clinical benefit as determined by the investigator, end of study, or other protocol-specified criteria for treatment discontinuation (whichever occurs first).

Drug: Everolimus 10mg daily

Interventions

Everolimus 10mg daily DRUG

An oral mTOR inhibitor

An Open-Label, Single-Arm Exploratory Study of Everolimus

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 and ≤65 years;
• No gender restrictions;
• Diagnosed with vascular malformation by MRI;
• No major surgery within the past 3 months;
• Able to swallow and retain oral medication, with no significant gastrointestinal abnormalities that may affect drug absorption, such as malabsorption syndrome, intestinal obstruction, or extensive gastrointestinal resection;
• Able to provide peripheral blood samples for biomarker testing at a central laboratory;
• Patients must have adequate organ and bone marrow function, and must not have received blood transfusions or any supportive treatments (e.g., cytokines or erythropoietin) to increase white blood cells, platelets, or hemoglobin levels within 7 days before screening tests:Absolute neutrophil count ≥1.0×10⁹/L;Hemoglobin ≥90 g/L; Platelets ≥100×10⁹/L;Total bilirubin ≤1.5× upper limit of normal (ULN), or ≤3.0× ULN for patients with Gilbert's syndrome;AST and ALT ≤2.5× ULN;Albumin ≥3 g/dL; Serum creatinine \<1.5× ULN or creatinine clearance ≥50 mL/min;Urine protein \<2+; if ≥2+, then 24-hour urine protein must be ≤1 g;Coagulation: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5× ULN.
• Patients must voluntarily sign the written informed consent form and be able to complete follow-up;
• For patients of childbearing potential: they must agree to use highly effective contraceptive methods, such as combined hormonal contraception, progestogen-only hormonal contraception associated with ovulation inhibition, intrauterine devices (IUDs), intrauterine hormonal systems (IUS), bilateral tubal occlusion, or partner vasectomy, or to practice sexual abstinence during the treatment period and for at least 90 days after the last dose. Male patients must agree to refrain from sperm donation for at least 90 days after the last dose.

You may not qualify if:

• Diagnosed with Hereditary Hemorrhagic Telangiectasia (HHT), Arteriovenous Malformation (AVM), or PTEN Hamartoma Tumor Syndrome (PHTS);
• Patients who have previously received any of the following treatments after birth: participation in other interventional clinical trials targeting cerebral cavernous malformations (CM);
• Presence of malignant tumors currently or within the past three years, except for curatively treated non-melanoma skin basal cell carcinoma, ductal carcinoma in situ of the breast, or cervical carcinoma in situ;
• Unable to undergo MRI scans and/or have contraindications for MRI (e.g., interference from prosthetics, orthodontic devices, etc., affecting target lesion volume analysis on MRI);
• Modified Rankin Scale (mRS) score of 5, respiratory failure, or currently experiencing severe bleeding requiring life-support treatment;
• Severe renal failure (e.g., creatinine clearance \\\[CrCl\] \< 30 mL/min, or significantly elevated serum creatinine not correctable by other means), recent history (within past 3 months) of renal failure or end-stage renal disease without effective treatment, or currently undergoing dialysis;
• Severe hepatic failure, including but not limited to: Child-Pugh Class C or higher, recent (within 3 months) uncontrolled symptoms related to hepatic failure such as ascites, jaundice, coagulopathy, or hepatic encephalopathy, or patients requiring liver transplantation;
• Currently using other immunosuppressants or patients with immunodeficiency;
• Patients requiring use of medications that interfere with or inhibit CYP3A4 enzyme activity, or medications such as cisapride or metoclopramide;
• Patients with dysphagia, active gastrointestinal disorders, malabsorption syndrome, or other conditions that may affect the absorption of the investigational drug;
• Interstitial pneumonitis, including clinically significant radiation pneumonitis;
• Severe asthma;
• Uncontrolled diabetes mellitus;
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements;
• First-degree relatives with a history of sudden cardiac death before the age of 50. First-degree relatives are defined as those with a direct bloodline, such as parents and children, grandparents and grandchildren, or maternal grandparents and maternal grandchildren;

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

the Department of Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital, Capital Medical University

Beijing, China

RECRUITING

MeSH Terms

Conditions

Vascular Malformations

Interventions

Everolimus

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Tao Hong, MD

CONTACT

+86-13810000653; hongtao.edu@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A total of 10 participants aged 18 to 65 years with a confirmed diagnosis of vascular malformation will be enrolled. Eligible patients must be deemed by the investigator to be unsuitable for effective surgical treatment. After screening, qualified participants will receive oral everolimus once daily in continuous cycles of 28 days. The daily dosage of everolimus for adult patients will be 10 mg. Treatment will continue until disease progression, intolerable toxicity, lack of clinical benefit as determined by the investigator, study termination, or any other pre-defined discontinuation criteria-whichever occurs first.

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 25, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available from 6 months following analysis and article publication
• Access Criteria: Future researchers must be from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept Department of Neurosurgery, Xuanwu Hospital, Capital Medical University's conditions for access

Locations

CN (1)