Clinical trial NCT03288168: Children's and Adolescents' Medulloblastoma Molecular Subgroups in China
Official title: Multi-center Retrospective Study on Clinical Features and Molecular Subgroups of Children and Adolescents With Medulloblastoma in China
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Medulloblastoma, Childhood
Keywords: Observation
Molecular Subgroup
NanoString
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
Collaborators: name: Children's Neuro-Oncology Group (CNOG)
First posted: 2017-09-19
Enrollment: 200
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children and adolescents from 0-18 y/o, diagnosed with Medulloblastoma in CNOG-MB001 study participated institutions in mainland China, with available detailed clinical records, full followup records and available tumor samples, fitting eligibility criteria, are enrolled in this study.

Brief summary: Recently, diagnosis and treatments for medulloblastoma becomes more complicated than before since the new World Health Organization (WHO) diagnosis criteria has put molecular marker onto an ever important position. Reports and studies revealed highly correlated connection between subgroups of medulloblastoma and patient outcomes. Children's Oncology Group (COG) has launched many new studies on molecular subgroups-based specific treatment trails. In China, children and adolescents with brain tumor have been treated variously for a long time in lack of standardized comprehensive treatments. Same poor situation in basic research and clinical studies makes the Chinese children with brain tumor hardly catch up with international level in molecular diagnosis and specific treatments. There are limited studies, which were conducted by immunohistochemistry for identifying medulloblastoma molecular subgroups, indicating the similar correlation of the subgroups and outcomes to world-wide reports. As the Children's Neuro-Oncology Group (CNOG) was established in China in May 2017, it makes studies from multiple centers in children's brain tumors become practical. And the availability of DNA methylation array, NanoString and other methods in medulloblastoma subgroup identification assures the quality of the method for this study.

Detailed description: Studies discovered that medulloblastoma is a group of tumors with different pathogenesis through different pathways, and majorly can be divided into four molecular subgroups. Moreover, multicenter retrospective studies from US, Canada and European Countries revealed that the molecular subgroup of medulloblastoma becomes an independent correlated risk factor for the patient outcomes. This finding made WHO classification of tumours of central nervous system consider the markers in molecular pathway be an ever important indicator in the new diagnosis criteria. In COG prospective studies for target therapies, subgroup distinguishing becomes indispensable, and the use of immunohistochemistry combined with NanoString, DNA methylation arrays or other molecular methods makes subgroup identification more reliable. In China, there are limited single institutional studies, which were all conducted by immunohistochemistry or polymerase chain reaction (PCR), on molecular sub-grouping of medulloblastoma, especially in pediatric patients. This multicenter retrospective study enrolls children and adolescents (0-18y/o) with primary medulloblastoma from CNOG member institutions across the country, with available paraffin embedded samples and reliable follow-up information, to assess the correlation of molecular subgroups of medulloblastoma and outcomes in Chinese population.

This multicenter study recruits eligible patients from CNOG member institutions. Data validation and verification is double conducted by each center and investigators in central data base. Case report form (CRF) was designed by principle investigator and will be modified in the period of uploading first 5 cases by each participated center. The estimated enrollment is 200 cases after sample size assessment. Descriptive statistical analysis, Two-Sample (Independent group) T-Test and one-way ANOVA will be used in epidemiological analysis. Cox-regression / Kaplan-Meier plot will be used in survival analysis. Chi-square test will be used to validate the test efficiency of immunohistochemistry and NanoString methods.

Eligibility criteria: Inclusion Criteria:

* Participants must have classical histology posterior fossa medulloblastoma as determined by institutional neuro-pathological evaluation.
* Participants must have tumor tissue samples (either paraffin embedded tissue block or frozen tissue) for NanoString test for distinguishing the molecular subgroups of medulloblastoma in Xinhua hospital affiliated to Shanghai Jiaotong University School of Medicine (SHXH).
* Participants must provide tumor tissue samples (either paraffin embedded tissue block or frozen tissue) for immunohistochemistry assessment in verifying the molecular subgroups of medulloblastoma, or conduct the same immunohistochemistry test according to central analysis in SHXH, and send the slides to SHXH for center reviewing.
* Diagnostic imaging (pre and post operation (OP) contrast MRI or CT, Post-OP imaging conducted within 72 hours, no later than 14 days) must be forwarded to SHXH for central review to confirm eligibility.
* Sufficient pathologic material must be available for central analysis and review in SHXH.
* The patients must have no previous radiotherapy or chemotherapy other than corticosteroids.
* Ability to understand and willingness to comply with follow-up visits.
* Life expectancy more than 4 weeks.

Exclusion Criteria:

* Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids.
* Tumor tissue sample not available for biological studies (from the initial diagnosis and/or relapse).
* Clinically significant unrelated systemic illness (e.g., serious infection or significant cardiac, pulmonary, hepatic, or other organ dysfunction) that would compromise the patient's ability to tolerate standard treatment or would likely interfere with study results.
* Patients obtained no radiation and/or chemo therapies are not excluded in this study since the nature history of the disease will also be evaluated.

Primary outcomes:
measure: Overall Survival
timeFrame: Follow-up for final survival period till 31 December 2017 or last available contact, whichever occurred first
Secondary outcomes:
measure: Event Free Survival
timeFrame: Follow-up for none-recurrence survival (metastasis/relapse) period till 31 December 2017 or last available contact, whichever occurred first.
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Fuzhou General Hospital of Nanjing Military Region
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong 999 Brain Hospital
state: Guangdong
city: Xi'an
country: China
facility: Xijing Hospital, Fourth Military Medical University
state: Shaanxi
city: Liaocheng
country: China
facility: Liaocheng People's Hospital
state: Shandong
city: Shanghai
country: China
facility: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Jie MA, MD, Phd
role: STUDY_CHAIR
References: