HemangioendotheliomaPhase 2NCT05324384
Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma
A Phase 2 study testing Sirolimus in people with Hemangioendothelioma, run by West China Hospital at 1 site in China.
Trial summary
The purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma. Read more about this study
- Who is it for?
- Ages Up to 14 years
- Conditions the study is for
- Hemangioendothelioma
- What is being tested?
- Sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 5 Apr 2022to 30 Nov 2025
- Phase
- Phase 2
- 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 Up to 14 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Presenting a KHE with the following characteristics:
- Male and female;
- Between 0 and 14 years of age;
- Diagnosis of KHE as determined by:
- Biopsy;
- Compatible MRI findings;
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- History and clinical features.
- Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
- Consent of parents (or the person with parental authority in families): signed and dated written informed consent.
Who cannot join
- Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
- Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
- Patients had a history of a major surgery within 2 weeks before enrollment;
- Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
- Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
- Concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
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- Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
- Patients with inadequate liver function:
- Total bilirubin higher than or equal to 1.5 × the upper limit of the normal (ULN) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the ULN for age.
- Patients with inadequate renal function:
- 0-5 years of age maximum serum creatinine (mg/dL) of 0.8; 6-10 years of age maximum serum creatinine (mg/dL) of 1.0; 11-14 years of age maximum serum creatinine (mg/dL) of 1.2;
- Adequate bone marrow function:
- Absolute neutrophil count lower than 1 × 109/L;
- History of a malignancy within 5 years;
- HIV infection or known immunodeficiency;
- Indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than IH;
- Patients with an inability to participate in or follow-up during the study treatment and assessment plan;
- Inability to give informed consent.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Yi Ji, MD, PhD, +86 28 85423453, jijiyuanyuan@163.com
Siyuan Chen, MD, PhD, +862885422215, siy_chen@163.com
About this study
Official title: Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma: a Randomized Controlled Trial
The purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma.
Read the detailed description
Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular neoplasm that occurs predominantly in infancy or early childhood, with an incidence of approximately 0.071/100,000. Currently, sirolimus is a promising treatment modality for KHE. Most scholars consider sirolimus blood concentration of 5-15 ng/ml to be an effective therapeutic concentration, while 10-15 ng/ml is the most commonly used blood concentration. However, long-term higher dose sirolimus treatment can cause some common adverse effects, such as oral mucositis which affects the quality of life of the patient. Finer control of the plasma concentration of sirolimus may contribute to the efficacy of treatment and reduce the incidence of complications. Previous studies have found good efficacy of low-dose sirolimus maintenance treatment for KHE. However, there is no high-level evidence to support this treatment strategy. Therefore, we conducted this study to find out whether an early reduction in sirolimus dose would benefit the prognosis of the patients.
- Conditions
- Hemangioendothelioma
- Being tested
- Sirolimus
- Keywords
- Kaposiform hemangioendothelioma, Hemangioendothelioma, Sirolimus
- Medical subject headings
- Hemangioendothelioma, Kaposiform Hemangioendothelioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin, Rapamune
Use of different doses of the same drug
| Study group | Role | What they receive |
|---|---|---|
| Low dose of sirolimus | Experimental | The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 6 months. Then, The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 6 months. Receives: Drug: Sirolimus |
| Regular dose of sirolimus | Active comparator | Sirolimus The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year. Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The changes in KHE volume
Response to therapy was measured by volumetric magnetic resonance imaging (MRI) analyses were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in KHE size were classified as further growth (increase of ≥10%), no change (<10% increase and <10% decrease), partial involution (decrease of ≥10% and <75%), nearly complete involution (decrease of ≥75% and <100%), or complete involution (100%).
Measured: 12 months.
Secondary outcomes (6)
Quality of life (QOL) in patients
Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Infant Scales (<2 years) or Pediatric Quality of Life Inventory (PedsQLTM) 4.0 Genetic Core Scales (2-18 years) were used.
Measured: Baseline, 6 months, 12 months.
Frequency of adverse events
Frequency of adverse events (e.g. gastrointestinal disorders, blood and lymphatic system disorders, metabolic disorders or other abnormal laboratory results, skin disorders and general disorders, etc.) collected by investigator and reported by parents. All adverse events were collected and graded according to Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE v4.0). The causality of the adverse event was determined by the multidisciplinary staff and was classified as definitively not related, probably not related, possibly related, probably related, or definitively related. Any dose reductions, interruptions, or cessations enacted at the discretion of the investigators were recorded.
Measured: Baseline, 6 months, 12 months.
The changes in the patient's musculoskeletal complication.
The severity of musculoskeletal complication was scored by using a 4-point scale: 1, asymptomatic or mild symptoms, clinical or diagnostic observations only; 2, moderate symptoms, limiting age-appropriate instrumental activities of daily living; 3, severe or medically significant symptoms, disabling or limiting self-care activities of daily living; and 4, life-threatening consequences, with urgent intervention indicated.
Measured: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of platelet counts.
Platelet counts
Measured: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of fibrinogen levels.
Fibrinogen levels
Measured: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of D-dimer levels.
D-dimer levels
Measured: Baseline, 3 monthss, 6 months, 9 months, 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2022
- Study start5 Apr 2022
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Nov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HemangioendotheliomaStudies of the same condition, open and under way.
- More trials run by West China HospitalThe 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yi Ji, West China Hospital
- Investigators
- Yi Ji, MD, PhD, Principal investigator, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05324384
- Sponsor's protocol ID
- 2022-405
- Status last verified
- Jan 2024
- First submitted
- 5 Apr 2022
- Last updated
- 24 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.
PubMed 32014025Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.
PubMed 31489702Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.
PubMed 28486787Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 2013 Jan;162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4.
PubMed 22871490Rossler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quere I, Baumgartner I, Niemeyer CM, Kapp FG. Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.
PubMed 33580918Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.
PubMed 35030255
Study at a glance
From the registry record, last updated by the sponsor on 24 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Different Doses of Sirolimus for the Maintenance Treatment of Kaposiform Hemangioendothelioma: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05324384
- Acronym / sponsor ID
- 2022-405
- Conditions
- Hemangioendothelioma
- Keywords
- Kaposiform hemangioendothelioma, Hemangioendothelioma, Sirolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Nov 2025 (estimated)
- First posted
- 12 Apr 2022 (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.
The purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma.
Detailed description
Kaposiform hemangioendothelioma (KHE) is a rare aggressive vascular neoplasm that occurs predominantly in infancy or early childhood, with an incidence of approximately 0.071/100,000. Currently, sirolimus is a promising treatment modality for KHE. Most scholars consider sirolimus blood concentration of 5-15 ng/ml to be an effective therapeutic concentration, while 10-15 ng/ml is the most commonly used blood concentration. However, long-term higher dose sirolimus treatment can cause some common adverse effects, such as oral mucositis which affects the quality of life of the patient. Finer control of the plasma concentration of sirolimus may contribute to the efficacy of treatment and reduce the incidence of complications. Previous studies have found good efficacy of low-dose sirolimus maintenance treatment for KHE. However, there is no high-level evidence to support this treatment strategy. Therefore, we conducted this study to find out whether an early reduction in sirolimus dose would benefit the prognosis of the patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose of sirolimus | Experimental | Drug: SirolimusThe plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 6 months. Then, The plasma trough concentration of sirolimus is maintained within the range of 5-8 ng/ml by adjusting sirolimus dose, for 6 months. |
| Regular dose of sirolimus | Active comparator | Drug: SirolimusSirolimus The plasma trough concentration of sirolimus is maintained within the range of 10-15 ng/ml by adjusting sirolimus dose, for 1 year. |
Who may qualify
- Ages
- Up to 14 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Male and female;
- Between 0 and 14 years of age;
- Diagnosis of KHE as determined by:
- Patients were required to have adequate liver, renal and bone marrow function, and absence of active infection
- Consent of parents (or the person with parental authority in families): signed and dated written informed consent.
Key exclusion criteria (18 listed)
- Patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog)
- Exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study;
- Patients had a history of a major surgery within 2 weeks before enrollment;
- Patients who have a history of treatment with sirolimus or other mTOR inhibitor;
- Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment;
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 |
|---|---|---|
| SirolimusAlso: Rapamycin, RapamuneUse of different doses of the same drug | Drug | Low dose of sirolimus, Regular dose of sirolimus |
Primary outcome
The changes in KHE volume
Time frame: 12 months.
Response to therapy was measured by volumetric magnetic resonance imaging (MRI) analyses were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in KHE size were classified as further growth (increase of ≥10%), no change (<10% increase and <10% decrease), partial involution (decrease of ≥10% and <75%), nearly complete involution (decrease of ≥75% and <100%), or complete involution (100%).
6 secondary outcomes
Quality of life (QOL) in patients
Time frame: Baseline, 6 months, 12 months.
Frequency of adverse events
Time frame: Baseline, 6 months, 12 months.
The changes in the patient's musculoskeletal complication.
Time frame: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of platelet counts.
Time frame: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of fibrinogen levels.
Time frame: Baseline, 3 monthss, 6 months, 9 months, 12 months.
The changes of D-dimer levels.
Time frame: Baseline, 3 monthss, 6 months, 9 months, 12 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jan 2024.
- Results publication: PubMed 32014025Ji Y, Chen S, Yang K, Xia C, Li L. Kaposiform hemangioendothelioma: current knowledge and future perspectives. Orphanet J Rare Dis. 2020 Feb 3;15(1):39. doi: 10.1186/s13023-020-1320-1.
- Results publication: PubMed 31489702Wang Z, Yao W, Sun H, Dong K, Ma Y, Chen L, Zheng S, Li K. Sirolimus therapy for kaposiform hemangioendothelioma with long-term follow-up. J Dermatol. 2019 Nov;46(11):956-961. doi: 10.1111/1346-8138.15076. Epub 2019 Sep 5.
- Results publication: PubMed 28486787Ji Y, Chen S, Xiang B, Li K, Xu Z, Yao W, Lu G, Liu X, Xia C, Wang Q, Li Y, Wang C, Yang K, Yang G, Tang X, Xu T, Wu H. Sirolimus for the treatment of progressive kaposiform hemangioendothelioma: A multicenter retrospective study. Int J Cancer. 2017 Aug 15;141(4):848-855. doi: 10.1002/ijc.30775. Epub 2017 May 26.
- Results publication: PubMed 22871490Croteau SE, Liang MG, Kozakewich HP, Alomari AI, Fishman SJ, Mulliken JB, Trenor CC 3rd. Kaposiform hemangioendothelioma: atypical features and risks of Kasabach-Merritt phenomenon in 107 referrals. J Pediatr. 2013 Jan;162(1):142-7. doi: 10.1016/j.jpeds.2012.06.044. Epub 2012 Aug 4.
- Results publication: PubMed 33580918Rossler J, Baselga E, Davila V, Celis V, Diociaiuti A, El Hachem M, Mestre S, Haeberli D, Prokop A, Hanke C, Loichinger W, Quere I, Baumgartner I, Niemeyer CM, Kapp FG. Severe adverse events during sirolimus "off-label" therapy for vascular anomalies. Pediatr Blood Cancer. 2021 Aug;68(8):e28936. doi: 10.1002/pbc.28936. Epub 2021 Feb 13.
- Results publication: PubMed 35030255Ji Y, Chen S, Zhou J, Yang K, Zhang X, Xiang B, Qiu T, Gong X, Zhang Z, Lan Y, Hu F, Kong F, Qiu Q, Zhang Y. Sirolimus plus prednisolone vs sirolimus monotherapy for kaposiform hemangioendothelioma: a randomized clinical trial. Blood. 2022 Mar 17;139(11):1619-1630. doi: 10.1182/blood.2021014027.
- Individual participant dataSharing planned: No
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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.
Yi Ji, MD, PhD principal investigator
West China Hospital
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 Sirolimus in people with Hemangioendothelioma, run by West China Hospital at 1 site in China.
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 18 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: status not confirmed, as of the sponsor's last update on 24 Jan 2024. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Yi Ji, MD, PhD (86 28 85423453, jijiyuanyuan@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The changes in KHE volume (time frame: 12 months.). 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 NCT05324384, which also lists 6 linked publications.
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 24 Jan 2024.