Neoplasms

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Angiofibroma

Neoplasms, Vascular Tissue

Neoplasms by Histologic Type

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Sirolimus

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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).

Igor m Vorozhtsov, MD,PhD

Department of Scientific Design and Controlled Clinical Trials

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.

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).

Prospective, open-label, non-randomized interventional study with a historical control group and pilot phase

Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (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)

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

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

proportion of patients with progression after sirolimus therapy initiation. Progression define as increase of JNA in volume \>20% from initial one.

The number of the severe bleeding cases in the post-surgery period in patients receiving sirolimus and in the historical control group.

The blood loss volume in the surgical intervention and postoperative period in patients receiving sirolimus and in the historical control group

ALL patients, received sirolimus: progression free survival ((recurrent JNA) and follow up (primary JNA))

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)	NCT05549167	Juvenile Nasoph...	Sirolimus	7 Years - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)	NCT05549167	Juvenile Nasoph...	Sirolimus	7 Years - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Efficacy and Safety of Sirolimus in Children and Adolescents With Juvenile Nasopharyngeal Angiofibroma (JNA)	NCT05549167	Juvenile Nasoph...	Sirolimus	7 Years - 18 Years	Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Spots Global Cancer Trial Database for juvenile nasopharyngeal angiofibroma