HemangiomaPhase 4NCT04077515

Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma

A Phase 4 study testing Sirolimus(0.8mg/m2) and Sirolimus(0.7mg/m2) in people with Hemangioma and Kaposiform Hemangioendothelioma, run by Children's Hospital of Fudan University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

to evaluate the safety and efficacy of Low-dose sirolimus in Kaposiform Hemangioendothelioma in Chinese children by a prospective, randomized open trial. Read more about this study

Who is it for?: Ages Up to 12 years
Conditions the study is for: Hemangioma, Kaposiform Hemangioendothelioma
What is being tested?: Sirolimus(0.8mg/m2) and Sirolimus(0.7mg/m2)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 92 participants
Where: 1 siteChina
Study dates: 1 May 2019to 31 Dec 2022
Phase: Phase 4
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 12 years
All sexes
No healthy volunteers
Child

Who may be able to join

Kaposiform Hemangioendotheliomas with or without Kasabach-Merritt Phenomenon.
0 - 12 years of age at the time of study entry.
Male or female.
Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.

Who cannot join

with hematological diseases.
with other solid tumors.
with hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency.
with tuberculosis,cytomegalovirus and Epstein-Barr virus infection before the treatment.

Trial locations and contacts

1 site in 1 country.

China1 site

Children's Hospital of Fudan University
Shanghai, 210012

Other trials in China

About this study

Official title: Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma:A Prospective, Randomized Open Trial

to evaluate the safety and efficacy of Low-dose sirolimus in Kaposiform Hemangioendothelioma in Chinese children by a prospective, randomized open trial.

Read the detailed description

The clinically commonly used dose of sirolimus for Kaposiform Hemangioendothelioma is 0.8 mg/m2 administered twice daily, and the blood concentration can be maintained at 10-15 ng/ml according to the pharmacokinetic formula.Related research reports that maintaining low blood concentration of sirolimus is effective in the treatment of certain vascular malformations and hemangioma, and complications are less. In the clinical practice, we found that the blood concentration was maintained at 7-10 ng/ml, and the patients still achieved good results and the chance of infections decreased. Therefore, this clinical trial was designed.In this trial, two different dosing regimens with corresponding blood concentration were designed to compare the safety and efficacy.In the high concentration group, the sirolimus dosage was adjusted monthly to achieve trough levels between 10 and 15 ng/mL(excluding 10 ng/ml), and it is still used at 0.8 mg/m2 administered twice daily.The low concentration group is 7-10 ng/ml (including 10 ng/ml), and the initial use of sirolimus is 0.7mg/m2 administered twice daily.The dose was adjusted according to the formula after two weeks.The follow-up and evaluation were performed according to a strictly established follow-up schedule after taking the drug.

Conditions: Hemangioma, Kaposiform Hemangioendothelioma
Being tested: Sirolimus(0.8mg/m2), Sirolimus(0.7mg/m2)
Keywords: Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome, Sirolimus, Rapamycin
Medical subject headings: Hemangioma, Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Sirolimus(0.8mg/m2)Drug
Also called Rapamycin
The initial use of sirolimus is 0.8mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.
Sirolimus(0.7mg/m2)Drug
Also called Rapamycin
The initial use of sirolimus is 0.7mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.

Study groups in NCT04077515
Study group	Role	What they receive
high blood concentration group	Active comparator	The blood concentration is maintained at 10-15ng/ml (not including 10ng/ml). Receives: Drug: Sirolimus(0.8mg/m2)
low blood concentration group	Experimental	The blood concentration is maintained at 7-10ng/ml (including 10ng/ml). Receives: Drug: Sirolimus(0.7mg/m2)

What is being measured

The primary outcome is the main question the study is designed to answer.

response to treatment
it is a variable outcome, including complete responses, partial response and no response.
The definitions are :
Complete Response：
1. platelets counts is greater than 100×10^9/L.
2. significant volume reduction is greater than 80%.
3. Fibrinogen levels at 2-4g/L.
4. The surface skin of the tumor is lighter or the tumor is softer significantly.
Partial Response:
1. platelets counts is greater than 40×10^9/L.
2. significant volume reduction is greater than 50%.
3. Fibrinogen levels at less than 50% reduction from baseline.
4. The surface skin of the tumor and palpation of the tumor have no change or less change.
No Response:
1. platelets counts is less than 40×10^9/L.
2. significant volume reduction is less than 50% or the tumor is bigger.
3. Fibrinogen levels at grater then 50% reduction from baseline.
4. The surface skin of the tumor is darker or the tumor is harder.
Measured: 1 year after taking the drug

Secondary outcomes (1)

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Monitoring patient's clinical biochemical indicators and symptoms
Measured: 1 year after taking the drug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 May 201931 Dec 2022

First posted4 Sep 2019
Study start1 May 2019
Primary completion10 Dec 2022
Study completion31 Dec 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for HemangiomaStudies of the same condition, open and under way.
More trials run by Children's Hospital of Fudan UniversityThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 92 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04077515
Sponsor's protocol ID: 2019-161
Status last verified: Jan 2023
First submitted: 25 Jun 2019
Last updated: 30 Jan 2023
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Drolet BA, Trenor CC 3rd, Brandao LR, Chiu YE, Chun RH, Dasgupta R, Garzon MC, Hammill AM, Johnson CM, Tlougan B, Blei F, David M, Elluru R, Frieden IJ, Friedlander SF, Iacobas I, Jensen JN, King DM, Lee MT, Nelson S, Patel M, Pope E, Powell J, Seefeldt M, Siegel DH, Kelly M, Adams DM. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma. J Pediatr. 2013 Jul;163(1):285-91. doi: 10.1016/j.jpeds.2013.03.080. No abstract available.
PubMed 23796341
Yoon HY, Hwang JJ, Kim DS, Song JW. Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis. Orphanet J Rare Dis. 2018 Nov 14;13(1):204. doi: 10.1186/s13023-018-0946-8.
PubMed 30428897
Kazmierczak D, Maliszewska A. [Disturbances of tooth and maxillary development in Down's syndrome and their treatment]. Czas Stomatol. 1986 Nov;39(11):755-9. No abstract available. Polish.
PubMed 2958244
Ozgonenel B, Martin A. Low-dose sirolimus controls recurrent iron deficiency in a patient with blue rubber bleb nevus syndrome. Pediatr Blood Cancer. 2015 Nov;62(11):2054-5. doi: 10.1002/pbc.25590. Epub 2015 Jul 1. No abstract available.
PubMed 26132912

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hemangioma trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Efficacy of Low-dose Sirolimus to Kaposiform Hemangioendothelioma:A Prospective, Randomized Open Trial
ClinicalTrials.gov ID: NCT04077515
Acronym / sponsor ID: 2019-161
Conditions: Hemangioma, Kaposiform Hemangioendothelioma
Keywords: Kaposiform Hemangioendothelioma, Kasabach-Merritt Syndrome, Sirolimus, Rapamycin
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 92 participants (actual)
Lead sponsor: Children's Hospital of Fudan UniversityUniversity, hospital or other
Study start: 1 May 2019 (actual)
Primary completion: 10 Dec 2022 (actual)
Study completion: 31 Dec 2022 (actual)
First posted: 4 Sep 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.

to evaluate the safety and efficacy of Low-dose sirolimus in Kaposiform Hemangioendothelioma in Chinese children by a prospective, randomized open trial.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
high blood concentration group	Active comparator	Drug: Sirolimus(0.8mg/m2)The blood concentration is maintained at 10-15ng/ml (not including 10ng/ml).
low blood concentration group	Experimental	Drug: Sirolimus(0.7mg/m2)The blood concentration is maintained at 7-10ng/ml (including 10ng/ml).

Who may qualify

Ages: Up to 12 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

Kaposiform Hemangioendotheliomas with or without Kasabach-Merritt Phenomenon.
0 - 12 years of age at the time of study entry.
Male or female.
Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.

Key exclusion criteria (4 listed)

with hematological diseases.
with other solid tumors.
with hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency.
with tuberculosis,cytomegalovirus and Epstein-Barr virus infection before the treatment.

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
Sirolimus(0.8mg/m2)Also: RapamycinThe initial use of sirolimus is 0.8mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.	Drug	high blood concentration group
Sirolimus(0.7mg/m2)Also: RapamycinThe initial use of sirolimus is 0.7mg/m2 administered twice daily.After two weeks of taking the drug, blood concentrations are measured and adjusted appropriately to maintain the targeted blood concentration.	Drug	low blood concentration group

Primary outcome

response to treatment
Time frame: 1 year after taking the drug
it is a variable outcome, including complete responses, partial response and no response. The definitions are : Complete Response： 1. platelets counts is greater than 100×10^9/L. 2. significant volume reduction is greater than 80%. 3. Fibrinogen levels at 2-4g/L. 4. The surface skin of the tumor is lighter or the tumor is softer significantly. Partial Response: 1. platelets counts is greater than 40×10^9/L. 2. significant volume reduction is greater than 50%. 3. Fibrinogen levels at less than 50% reduction from baseline. 4. The surface skin of the tumor and palpation of the tumor have no change or less change. No Response: 1. platelets counts is less than 40×10^9/L. 2. significant volume reduction is less than 50% or the tumor is bigger. 3. Fibrinogen levels at grater then 50% reduction from baseline. 4. The surface skin of the tumor is darker or the tumor is harder.

1 secondary outcome

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 1 year after taking the drug

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
Background: PubMed 23796341Drolet BA, Trenor CC 3rd, Brandao LR, Chiu YE, Chun RH, Dasgupta R, Garzon MC, Hammill AM, Johnson CM, Tlougan B, Blei F, David M, Elluru R, Frieden IJ, Friedlander SF, Iacobas I, Jensen JN, King DM, Lee MT, Nelson S, Patel M, Pope E, Powell J, Seefeldt M, Siegel DH, Kelly M, Adams DM. Consensus-derived practice standards plan for complicated Kaposiform hemangioendothelioma. J Pediatr. 2013 Jul;163(1):285-91. doi: 10.1016/j.jpeds.2013.03.080. No abstract available.
Background: PubMed 30428897Yoon HY, Hwang JJ, Kim DS, Song JW. Efficacy and safety of low-dose Sirolimus in Lymphangioleiomyomatosis. Orphanet J Rare Dis. 2018 Nov 14;13(1):204. doi: 10.1186/s13023-018-0946-8.
Background: PubMed 2958244Kazmierczak D, Maliszewska A. [Disturbances of tooth and maxillary development in Down's syndrome and their treatment]. Czas Stomatol. 1986 Nov;39(11):755-9. No abstract available. Polish.
Background: PubMed 26132912Ozgonenel B, Martin A. Low-dose sirolimus controls recurrent iron deficiency in a patient with blue rubber bleb nevus syndrome. Pediatr Blood Cancer. 2015 Nov;62(11):2054-5. doi: 10.1002/pbc.25590. Epub 2015 Jul 1. No abstract available.
Individual participant dataSharing planned: No

Related trials for Hemangioma

Not yet recruitingObservational study
Observation Study on the Efficacy and Safety of Hepatic Artery Embolization Combined With Radiofrequency Ablation for Hepatic Hemangioma: The Impact of Different Treatment Intervals
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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.

Kai Li, MD, PhD principal investigator

Children's Hospital of Fudan University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Sirolimus(0.8mg/m2) and Sirolimus(0.7mg/m2) in people with Hemangioma and Kaposiform Hemangioendothelioma, run by Children's Hospital of Fudan University 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 4 inclusion and 4 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: finished, as of the sponsor's last update on 30 Jan 2023. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 to treatment (time frame: 1 year after taking the drug). 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 NCT04077515, which also lists 4 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 30 Jan 2023.