Juvenile Nasopharyngeal AngiofibromaPhase 3NCT05549167
Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)
A Phase 3 study testing Sirolimus in people with Juvenile Nasopharyngeal Angiofibroma, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
Trial summary
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. Read more about this study
- Who is it for?
- Ages 7 to 18 years, men only
- Conditions the study is for
- Juvenile Nasopharyngeal Angiofibroma
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 117 participants
- Where
- 1 siteRussia
- Study dates
- 30 May 2022to 30 Dec 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 7 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Confirmed diagnosis of JNA.
- Male gender.
- Age 7-18 years.
- Signed informed consent of the parents or the official representative for patients under 14 years of age, the patient and the patient's parents for persons from 14 to 18 years of age.
- Adequate liver and kidney function.
- Patients with primary JNA
Show all 11Show fewer
- Patients with tumor volume according to MRI >35 ml. Group A1 (Extended phase:) - patients with decrease or stable tumor volume or an increase in tumor volume < 20 %, after 3 months of sirolimus therapy.
- Group A2 (Extended phase:)- patients with an increase in tumor volume> 20 % after 3 months of sirolimus therapy or the presence of other indications for surgical treatment, according to the investigator opinion.
- Historical control group - patients with diagnosed primary JNA, received treatment in Dmitry Rogachev's Center in the period from January 1, 2013 to April 15, 2022.
- Group B RECCURRENT JNA, Patients with recurrent JNA after primary surgery, who have not previously received sirolimus therapy.
- Historical control group - patients with diagnosed recurrent JNA, received treatment in Dmitry Rogachev' s Center in the period from January 1, 2013 to April 15, 2022.
Who cannot join
- Hypersensitivity to sirolimus or its analogues. The presence of acute or chronic infections, including opportunistic infections.
- Hepatic and/or renal insufficiency. The need for concomitant use of inducers (e.g. rifampicin, rifabutin) or inhibitors (e.g. ketoconazole) of the cytochrome CYP3A4 system Previous therapy with sirolimus or other mTOR inhibitors. Indications to palliative therapy, according to investigator's opinion. Participation in other clinical trials.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Russia1 site, 1 recruiting
- Recruiting
Research Institute of Pediatric Hematology, Oncology and Immunology
Moscow, 117997
Department of Scientific Design and Controlled Clinical Trials, +7 495 287 65 70 ext. 5551, lena.smirnova@fccho-moscow.ru
About this study
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. mTOR signaling way demonstrated to be involved in regulation of growth and angiogenesis of JNA. Sirolimus, as mTOR inhibitor, is a potential target JNA therapy.
The main purpose of the study is to evaluate the efficacy and safety of sirolimus in children and adolescents with primary or recurrent JNA. Efficacy will be estimated based on dynamics of the JNA progression. Historical control group will be used for comparison as standard therapy.
Due to limited experience of sirolimus in JNA in routine practice, study should be conducted in 2 phases: pilot and extended. Decision regarding extended phase will be based on the results of pilot phase.
Read the detailed description
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. Inhibition of mTOR signaling proved to be an important point in inhibition of JNA growth and vascularization. Sirolimus (rapamun) is an mTOR inhibitor, still data on sirolimus efficacy and safety in JNA is limited to few clinical cases.
The main purpose of the study is to evaluate the efficacy and safety of sirolimus in children and adolescents with primary or recurrent JNA. Historical control will be used for comparison as standard treatment.
Due to limited experience of sirolimus in JNA in routine practice, study should be conducted in 2 phases: pilot and extended.
The duration of the pilot phase is 3 months. Decision regarding conducting of extended phase will be based on the response to treatment in pilot phase. Response to treatment defined as a reduction of the JNA volume or stable volume or an increase in volume < 20% from the initial one.
In the extended period, duration of treatment for patients with primary JNA will be determined by the response to treatment. In case of the response to the therapy, treatment duration will be up to 9 months (3 courses by 3 months each). In case of JNA increase in volume more than 20% from the initial one (control time points 3 and 6 months), sirolimus therapy will be discontinued and surgical intervention to be provided (according to the investigator's decision). After completion of 9 months' treatment period, all patients with primary JNA will receive surgical treatment. The duration of follow up is 3 years In the group of patients with relapse or progression of JNA, therapy will continue up to 3 years or until loss of the response to the therapy (which the earliest).
Optimal individual dosage of sirolimus will be determined under control of concentration in blood serum. Sirolimus therapeutic concentration - 5-15 ng/ml. Blood samples will be collected until therapeutic concertation will be achieved in 2 consecutive samples, but no more than 4 samples (on the 4th, 7th, 10th, 14th days of sirolimus admission).
- Conditions
- Juvenile Nasopharyngeal Angiofibroma
- Being tested
- Sirolimus
- Keywords
- Juvenile nasopharyngeal angiofibroma, JNA, sirolimus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Sirolimus 0,8 mg/m2, but <2 mg per day, once a day (QD), per os, oral solution, 1mg/ml, 60 ml Optimal individual dosage of sirolimus will be determined under control of concentration in blood serum. Therapeutic concentration - 5-15 ng/ml. Blood samples will be collected until therapeutic concertation will be achieved in 2 consecutive samples, but no more than 4 samples (on the 4th, 7th, 10th, 14th days of admission).
| Study group | Role | What they receive |
|---|---|---|
| intervention/treatment | Experimental | Not described Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with JNA with positive dynamics
The proportion of patients with JNA with positive dynamics (reduction of tumor volume or stabilization of tumor volume or increase in tumor volume < 20% of the initial)
Measured: 3 months from study enrollment
Secondary outcomes (16)
The proportion of patients with JNA with positive dynamics
Primary JNA: The proportion of patients with JNA with positive dynamics (reduction of tumor volume or stabilization of tumor volume or increase in tumor volume < 20% of the initial one
Measured: 6 months from study enrollment
The proportion of patients with JNA with positive dynamics
The proportion of patients with JNA with positive dynamics (reduction of tumor volume or stabilization of tumor volume or increase in tumor volume < 20% of the initial one
Measured: 9 months from study enrollment
proportion of patients with progression after sirolimus therapy initiation
proportion of patients with progression after sirolimus therapy initiation. Progression define as increase of JNA in volume >20% from initial one.
Measured: 3, 6, 9 months from study enrollment
The number and proportion (%) of patients receiving sirolimus without tumor progression in post-surgery catamnesis.
Measured: 6, 12, 18, 24, 30, 36 months of post-surgery catamnesis.
Primary JNA: The number of the severe bleeding cases in the post-surgery period
The number of the severe bleeding cases in the post-surgery period in patients receiving sirolimus and in the historical control group.
Measured: up to 6 days after surgery intervention
The blood loss volume in the surgical intervention and postoperative period
The blood loss volume in the surgical intervention and postoperative period in patients receiving sirolimus and in the historical control group
Measured: up to 6 days after surgery intervention
Number and % of patients requiring hem transfusions in the surgical intervention and/or postoperative periods in patients receiving sirolimus and in the historical control group
Measured: up to 6 days after surgery intervention
amount of patients required embolization and completeness of embolization in patients receiving sirolimus and in the historical control group.
Measured: 1 day of surgery intervention
The proportion of patients (%) with complete and partial removal of JNA in patients treated with sirolimus and in the historical control group.
Measured: 1 day of surgery intervention
Recurrent JNA: The number and proportion (%) of patients with tumor progression (tumor growth in the same location)
Measured: 6, 9, 15, 21, 27 and 33 months of sirolimus therapy.
Recurrent JNA: The number and proportion (%) of patients with tumor recurrence (tumor growth in new location) treated with sirolimus and in the historical control group
Measured: 6, 9, 15, 21, 27 and 33 months of sirolimus therapy.
Recurrent JNA: The number and proportion (%) of patients required surgery intervention or radiotherapy in patients received sirolimus and in the historical control group
Measured: 33 months of sirolimus treatment
ALL patients, received sirolimus: progression free survival
ALL patients, received sirolimus: progression free survival ((recurrent JNA) and follow up (primary JNA))
Measured: up to 36 months of treatment
ALL patients, received sirolimus: quality of nasal breath by NOSE questionnaire
Measured: For primary JNA: day 7, 14, month 1, 6 , 9 of sirolimus treatment and months 6, 12, 24, 36 of follow up
ALL patients, received sirolimus: quality of nasal breath by NOSE questionnaire
Measured: For recurrent JNA - up to 33 months of sirolimus treatment
ALL patients, received sirolimus: safety monitoring frequency and severity of AEs
Measured: For recurrent JNA - up to 33 months of sirolimus treatmen
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2022
- Study start30 May 2022
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Juvenile Nasopharyngeal AngiofibromaStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective, open-label, non-randomized interventional study with a historical control group and pilot phase
- Masking
- None (open label)
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and Immunology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05549167
- Sponsor's protocol ID
- NCHPOI-2022--09
- Status last verified
- Aug 2022
- First submitted
- 29 Aug 2022
- Last updated
- 22 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)
- ClinicalTrials.gov ID
- NCT05549167
- Acronym / sponsor ID
- NCHPOI-2022--09
- Conditions
- Juvenile Nasopharyngeal Angiofibroma
- Keywords
- Juvenile nasopharyngeal angiofibroma, JNA, sirolimus
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- Federal Research Institute of Pediatric Hematology, Oncology and ImmunologyUniversity, hospital or other
- Study start
- 30 May 2022 (actual)
- Primary completion
- 30 Sep 2029 (estimated)
- Study completion
- 30 Dec 2029 (estimated)
- First posted
- 22 Sep 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.
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. mTOR signaling way demonstrated to be involved in regulation of growth and angiogenesis of JNA. Sirolimus, as mTOR inhibitor, is a potential target JNA therapy.
The main purpose of the study is to evaluate the efficacy and safety of sirolimus in children and adolescents with primary or recurrent JNA. Efficacy will be estimated based on dynamics of the JNA progression. Historical control group will be used for comparison as standard therapy.
Due to limited experience of sirolimus in JNA in routine practice, study should be conducted in 2 phases: pilot and extended. Decision regarding extended phase will be based on the results of pilot phase.
Detailed description
Juvenile nasopharyngeal angiofibroma (JNA) is a pathologically benign yet locally aggressive and destructive tumor that develops in the choana and nasopharynx. Historical treatment of JNA has included embolization, surgical resection, and radiation. Inhibition of mTOR signaling proved to be an important point in inhibition of JNA growth and vascularization. Sirolimus (rapamun) is an mTOR inhibitor, still data on sirolimus efficacy and safety in JNA is limited to few clinical cases.
The main purpose of the study is to evaluate the efficacy and safety of sirolimus in children and adolescents with primary or recurrent JNA. Historical control will be used for comparison as standard treatment.
Due to limited experience of sirolimus in JNA in routine practice, study should be conducted in 2 phases: pilot and extended.
The duration of the pilot phase is 3 months. Decision regarding conducting of extended phase will be based on the response to treatment in pilot phase. Response to treatment defined as a reduction of the JNA volume or stable volume or an increase in volume < 20% from the initial one.
In the extended period, duration of treatment for patients with primary JNA will be determined by the response to treatment. In case of the response to the therapy, treatment duration will be up to 9 months (3 courses by 3 months each). In case of JNA increase in volume more than 20% from the initial one (control time points 3 and 6 months), sirolimus therapy will be discontinued and surgical intervention to be provided (according to the investigator's decision). After completion of 9 months' treatment period, all patients with primary JNA will receive surgical treatment. The duration of follow up is 3 years In the group of patients with relapse or progression of JNA, therapy will continue up to 3 years or until loss of the response to the therapy (which the earliest).
Optimal individual dosage of sirolimus will be determined under control of concentration in blood serum. Sirolimus therapeutic concentration - 5-15 ng/ml. Blood samples will be collected until therapeutic concertation will be achieved in 2 consecutive samples, but no more than 4 samples (on the 4th, 7th, 10th, 14th days of sirolimus admission).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective, open-label, non-randomized interventional study with a historical control group and pilot phase
| Arm | Type | Receives |
|---|---|---|
| intervention/treatment | Experimental | Drug: Sirolimus |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Confirmed diagnosis of JNA.
- Male gender.
- Age 7-18 years.
- Signed informed consent of the parents or the official representative for patients under 14 years of age, the patient and the patient's parents for persons from 14 to 18 years of age.
- Adequate liver and kidney function.
Key exclusion criteria (2 listed)
- Hypersensitivity to sirolimus or its analogues. The presence of acute or chronic infections, including opportunistic infections.
- Hepatic and/or renal insufficiency. The need for concomitant use of inducers (e.g. rifampicin, rifabutin) or inhibitors (e.g. ketoconazole) of the cytochrome CYP3A4 system Previous therapy with sirolimus or other mTOR inhibitors. Indications to palliative therapy, according to investigator's opinion. Participation in other clinical trials.
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 |
|---|---|---|
| SirolimusSirolimus 0,8 mg/m2, but <2 mg per day, once a day (QD), per os, oral solution, 1mg/ml, 60 ml Optimal individual dosage of sirolimus will be determined under control of concentration in blood serum. Therapeutic concentration - 5-15 ng/ml. Blood samples will be collected until therapeutic concertation will be achieved in 2 consecutive samples, but no more than 4 samples (on the 4th, 7th, 10th, 14th days of admission). | Drug | intervention/treatment |
Primary outcome
The proportion of patients with JNA with positive dynamics
Time frame: 3 months from study enrollment
The proportion of patients with JNA with positive dynamics (reduction of tumor volume or stabilization of tumor volume or increase in tumor volume < 20% of the initial)
16 secondary outcomes
The proportion of patients with JNA with positive dynamics
Time frame: 6 months from study enrollment
The proportion of patients with JNA with positive dynamics
Time frame: 9 months from study enrollment
proportion of patients with progression after sirolimus therapy initiation
Time frame: 3, 6, 9 months from study enrollment
The number and proportion (%) of patients receiving sirolimus without tumor progression in post-surgery catamnesis.
Time frame: 6, 12, 18, 24, 30, 36 months of post-surgery catamnesis.
Primary JNA: The number of the severe bleeding cases in the post-surgery period
Time frame: up to 6 days after surgery intervention
The blood loss volume in the surgical intervention and postoperative period
Time frame: up to 6 days after surgery intervention
Number and % of patients requiring hem transfusions in the surgical intervention and/or postoperative periods in patients receiving sirolimus and in the historical control group
Time frame: up to 6 days after surgery intervention
amount of patients required embolization and completeness of embolization in patients receiving sirolimus and in the historical control group.
Time frame: 1 day of surgery intervention
The proportion of patients (%) with complete and partial removal of JNA in patients treated with sirolimus and in the historical control group.
Time frame: 1 day of surgery intervention
Recurrent JNA: The number and proportion (%) of patients with tumor progression (tumor growth in the same location)
Time frame: 6, 9, 15, 21, 27 and 33 months of sirolimus therapy.
Recurrent JNA: The number and proportion (%) of patients with tumor recurrence (tumor growth in new location) treated with sirolimus and in the historical control group
Time frame: 6, 9, 15, 21, 27 and 33 months of sirolimus therapy.
Recurrent JNA: The number and proportion (%) of patients required surgery intervention or radiotherapy in patients received sirolimus and in the historical control group
Time frame: 33 months of sirolimus treatment
ALL patients, received sirolimus: progression free survival
Time frame: up to 36 months of treatment
ALL patients, received sirolimus: quality of nasal breath by NOSE questionnaire
Time frame: For primary JNA: day 7, 14, month 1, 6 , 9 of sirolimus treatment and months 6, 12, 24, 36 of follow up
ALL patients, received sirolimus: quality of nasal breath by NOSE questionnaire
Time frame: For recurrent JNA - up to 33 months of sirolimus treatment
ALL patients, received sirolimus: safety monitoring frequency and severity of AEs
Time frame: For recurrent JNA - up to 33 months of sirolimus treatmen
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Juvenile Nasopharyngeal Angiofibroma, run by Federal Research Institute of Pediatric Hematology, Oncology and Immunology at 1 site in Russia.
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 11 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 22 Sep 2022. 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 Russia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Igor m Vorozhtsov, MD,PhD (+79252019332, dr.vorozhtsov@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The proportion of patients with JNA with positive dynamics (time frame: 3 months from study enrollment). 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 22 Sep 2022.