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

NCT05549167 | Recruiting Phase 3

• 1 other identifier: NCHPOI-2022--09
• Study Type: interventional
• Target: 117
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Juvenile Nasopharyngeal Angiofibroma

Keywords

Juvenile nasopharyngeal angiofibroma; JNA; sirolimus

Outcome Measures

Primary Outcomes (1)

• 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)

  3 months from study enrollment

Secondary Outcomes (16)

• The proportion of patients with JNA with positive dynamics

  6 months from study enrollment

• The proportion of patients with JNA with positive dynamics

  9 months from study enrollment

• proportion of patients with progression after sirolimus therapy initiation

  3, 6, 9 months from study enrollment

• The number and proportion (%) of patients receiving sirolimus without tumor progression in post-surgery catamnesis.

  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

  up to 6 days after surgery intervention

Other Outcomes (1)

• Optimization of sirolumus dosage regime: Control of sirolimus 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 Arms (1)

intervention/treatment

EXPERIMENTAL

Drug: Sirolimus

Interventions

Sirolimus DRUG

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).

intervention/treatment

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

Research Institute of Pediatric Hematology, Oncology and Immunology

Moscow, 117997, Russia

RECRUITING

MeSH Terms

Interventions

Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Igor m Vorozhtsov, MD,PhD

CONTACT

+79252019332; dr.vorozhtsov@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: August 29, 2022
• First Posted: September 22, 2022
• Study Start: May 30, 2022
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): December 30, 2029
• Last Updated: September 22, 2022

Record last verified: 2022-08

Locations

RU (1)