Clinical trial NCT05711992: Rare Embryonal Tumors of the Central Nervous System: International Registry
Official title: Rare Embryonal Tumors of the Central Nervous System: International Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Embryonal Tumor
Lead sponsor: Immune Oncology Research Institute
Sponsor class: OTHER
First posted: 2023-02-03
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All patients diagnosed with rare embryonal tumors

Brief summary: Central nervous system (CNS) tumors are the most common solid malignancies among children. Although some types of CNS tumors like medulloblastomas and low-grade gliomas are widespread and well-studied, there is a huge number of rare diseases that need further research. This international registry aims to establish a large multicenter database of pediatric and young adult patients with rare embryonal tumors of the central nervous system and describe the clinical presentations, diagnostics, treatment regimens, and outcomes. Embryonal tumors with multilayered rosettes (ETMR), FOXR2-activated CNS neuroblastoma, cribriform neuroepithelial tumor, and CNS tumor with BCOR internal tandem duplication are extremely rare embryonal tumors some of which were first described in the last edition of the World Health Organization (WHO) Classification of Tumors of the Central Nervous System. Objectives of the registry are 1) to evaluate prognostic factors, 2) to identify diagnostic and treatment gaps, 3) to investigate the characteristics and outcome of the disease with different treatment regimens, and 4) to generate data-based prospective diagnostic and treatment recommendations.

Detailed description: CNS tumors are the most common solid malignancies and the leading cause of children's cancer-related mortality. Embryonal tumors account for approximately 20-25% of all primary CNS tumors in children. Although medulloblastomas are the most commonly diagnosed malignant brain tumors, other embryonal tumors are relatively rare. Several studies of rare embryonal tumors have been published, but the number of included patients is generally small. Diagnosis of different subtypes of rare embryonal tumors can be extremely challenging. Because of limited data, there are no standard treatment recommendations for patients with rare embryonal tumors.

Embryonal tumors with multilayered rosettes (ETMR), FOXR2-activated CNS neuroblastoma, cribriform neuroepithelial tumor, CNS tumor with BCOR internal tandem duplication, and embryonal tumors not otherwise specified/not elsewhere classified (NOS/NEC) are extremely rare. Moreover, FOXR2-activated CNS neuroblastoma, cribriform neuroepithelial tumor, and CNS tumor with BCOR internal tandem duplication were first described in the fifth edition of the WHO Classification of Tumors of the Central Nervous System, published in 2021. Because of the rarity of these tumors, randomized controlled clinical trials are extremely complicated to conduct. Considering the lack of studies from low- and middle-income countries (LMICs) it is not excluded that cases of rare embryonal tumors are more common than have been described in the literature. Hence, evidence can be generated through registry studies.

This is a multicenter international retrospective and prospective registry to collect and analyze data from pediatric and young adult patients diagnosed with rare CNS embryonal tumors. Patients will be recruited directly by participating centers and national study groups. Participating centers will collect and verify the informed consent of all prospective patients enrolled at their centers.

Patients diagnosed with rare embryonal tumors of the CNS (ETMR, FOXR2-activated CNS neuroblastoma, cribriform neuroepithelial tumor, CNS tumor with BCOR internal tandem duplication, embryonal tumors NOS/NEC) since 01.01.2010 will be included. ETMR has been included in the WHO classification of CNS tumors since 2016 and encompasses three morphologically distinct embryonal tumors (Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL)) that were previously classified as CNS primitive neuroectodermal tumors (CNS-PNETs). These histological subtypes should also be included in the study. Considering the lack of molecular genetic tests done among retrospective cases, the investigators will also include all patients diagnosed with neuroblastoma and ganglioneuroblastoma.

The following data will be collected through questionnaires:

1. Patient characteristics
2. Characteristics of rare CNS embryonal tumors
3. Details of the diagnosis and treatment
4. Complications and late effects of treatment
5. Outcomes
6. Follow-up information

Quality control and data management will be conducted by the Immune Oncology Research Institute.

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with rare embryonal tumors of CNS since 01.01.2010:

  * ETMR (including embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL) and medulloepithelioma (MEPL) which were previously classified as CNS-PNETs)
  * FOXR2-activated CNS neuroblastoma
  * cribriform neuroepithelial tumor
  * CNS tumor with BCOR internal tandem duplication
  * all patients diagnosed with neuroblastoma and ganglioneuroblastoma with no molecular genetic tests available
* Patients ≤ 25 years of age
* Signed informed consent form for prospective patients ≥ 18 years of age
* Signed parental permission and child assent forms for prospective patients \< 18 years of age

Exclusion Criteria:

• CNS metastases of extracranial embryonal tumors

Primary outcomes:
measure: 3-year overall survival
timeFrame: 3 years
measure: 5-year overall survival
timeFrame: 5 years
Secondary outcomes:
measure: Complete remission rate
timeFrame: 5 years
measure: 3-year event-free survival
timeFrame: 3 years
measure: 5-year event-free survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Hematology Center named after prof. R. Yeolyan
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario (CHEO)
city: Budapest
country: Hungary
facility: Semmelweis University
city: New Delhi
country: India
facility: National Cancer Institute, All India Institutes of Medical Sciences
city: Tehran
country: Iran, Islamic Republic of
facility: Oncology Department of Golestan hospital
city: Rome
country: Italy
facility: IRCCS Istituto Ospedale Pediatrico Bambino Gesù
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara "Dr. Juan I. Menchaca"
city: Mexico City
country: Mexico
facility: Centro Médico ABC
city: Bellavista
country: Peru
facility: Hospital Nacional Alberto Sabogal Sologuren - EsSalud
city: Lima
country: Peru
facility: Hospital Nacional Edgardo Rebagliati Martins
city: Taichung
country: Taiwan
facility: China Medical University Children's Hospital
Study officials:
affiliation: Immune Oncology Research Institute, Yerevan, Armenia
name: Julieta Hoveyan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Immune Oncology Research Institute, Yerevan, Armenia
name: Ruzanna Papyan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Immune Oncology Research Institute, Yerevan, Armenia
name: Gevorg Tamamyan, MD, PhD, DSc
role: STUDY_DIRECTOR
References: