Molecular Epidemiology of Pediatric Germ Cell Tumors

Recruiting

• Conditions: Late Effects; Embryonal Carcinoma; Pediatric Germ Cell Tumor; Germ Cell Tumor; Germinoma; Teratoma; Yolk Sac Tumor; Choriocarcinoma; Mixed Germ Cell Tumor
• Interventions: Other: Questionnaire Administration; Other: Tumor Specimen Collection; Other: Germline DNA Samples; Procedure: Blood Sample Collection

• Registration Number: NCT05564026
• Lead Sponsor: Children's Oncology Group

Brief Summary

A Non-Therapeutic Study that aims to establish a cohort of GCT survivors to understand short term and long-term adverse effects of treatment and to conduct molecular analyses to improve risk stratification.

Detailed Description

PRIMARY OBJECTIVES:

I. Establish a survivorship cohort for pediatric and adolescent GCT comprised of participants from AEPI10N1 and APEC14B1 to assess short term and long-term adverse events associated with GCT treatment.

II. Compare somatic variation by tumor histology to identify molecular signatures that improve prognostic risk stratification.

III. Identify methylation patterns that predict poor clinical outcomes, including disease relapse and death.

OUTLINE:

Medical records from pediatric and adolescent Germ Cell Tumor (GCT) participants from AEPI10N1 and APEC14B1 will be used to obtain treatment information and validate self-reported outcomes. Paired normal and tumor samples will be used to evaluate single nucleotide variants, indels, copy number variations, and DNA methylation patterns. Ototoxicity will be determined by central review of audiogram files obtained from the treating institutions and self-reported based on questionnaire data.

Study Timeline

• Study First Submitted: 2022-09-29
• Study First Submitted QC: 2022-09-29
• Study First Posted: 2022-10-03
• Study Start: 2023-04-12
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-27
• Last Update Posted: 2024-09-30
• Primary Completion: 2027-06-30
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1151

Inclusion Criteria

• Cases will be eligible for the study if they have a primary diagnosis of GCT including germinoma (ICCC code105 9060-9065), teratoma (9080-9084), embryonal carcinoma (9070-9072), yolk sac tumor (9071), choriocarcinoma (9100, 9103, 9104), and mixed GCT (9085, 9101, 9102, 9105) in all sites including the brain.
• The patient must be enrolled on APEC14B1 with consent to future contact or enrolled in AEPI10N1 with consent for future contact (N=827). Patients enrolled in AEPI10N1 were recruited from ACCRN07. All patients must be registered with COG by a North American member institution. Note: (history of) treatment on a COG therapeutic trial is not required.
• Patients must be diagnosed at < 20 years of age at the time of GCT diagnosis. Study participants will be followed over time in the survivorship study so there is no maximum age for participation.
• Participants must be able to complete study related documents in English or Spanish.
• All patients and/or their parents or legal guardians must provide informed consent. Assent will be obtained for participants between the ages of 8-17 years.
• All institutional, FDA, and NCI requirements for human studies must be met.

Exclusion Criteria

• Participants from AEPI10N1 who did not consent to future contact. Patients who do not meet the eligibility criteria described above or cannot complete study materials in English or Spanish

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ancillary-Correlative	Tumor Specimen Collection	Children and adolescents with a germ cell tumor, previously enrolled on APEC14B1 or AEPI10N1 who allow access to medical records (including audiograms), grant permission to: evaluate of all of their DNA, place their genetic and health information in scientific databanks, and collect a blood sample at a routine clinic/home visit, as well as complete a questionnaire about your health and quality of life since treatment.
Ancillary-Correlative	Questionnaire Administration	Children and adolescents with a germ cell tumor, previously enrolled on APEC14B1 or AEPI10N1 who allow access to medical records (including audiograms), grant permission to: evaluate of all of their DNA, place their genetic and health information in scientific databanks, and collect a blood sample at a routine clinic/home visit, as well as complete a questionnaire about your health and quality of life since treatment.
Ancillary-Correlative	Germline DNA Samples	Children and adolescents with a germ cell tumor, previously enrolled on APEC14B1 or AEPI10N1 who allow access to medical records (including audiograms), grant permission to: evaluate of all of their DNA, place their genetic and health information in scientific databanks, and collect a blood sample at a routine clinic/home visit, as well as complete a questionnaire about your health and quality of life since treatment.
Ancillary-Correlative	Blood Sample Collection	Children and adolescents with a germ cell tumor, previously enrolled on APEC14B1 or AEPI10N1 who allow access to medical records (including audiograms), grant permission to: evaluate of all of their DNA, place their genetic and health information in scientific databanks, and collect a blood sample at a routine clinic/home visit, as well as complete a questionnaire about your health and quality of life since treatment.

Primary Outcome Measures

Name	Time	Method
Methylation	Up to 5 years	Compare the association between DNA methylation patterns and relapse or death. Mixed-effects regression models will be used to test for association between methylation beta values and poor outcomes. The outcome will be defined as a binary variable with a value of one if the patient experienced a relapse or death event and zero otherwise.
Somatic Mutations	Up to 5 years	Compare somatic variation by tumor histology to identify molecular signatures that improve prognostic risk stratification. Somatic mutations will be identified by comparing tumor samples to normal samples. Risk stratification will be based on event free survival, defined as the time from diagnosis to relapse or death.
Ototoxicity	Up to 5 years	Ototoxicity as determined by central review of end of therapy audiograms will serve as the primary outcome variable for analyses. Current ototoxicity will be assessed using an app-based hearing assessment. For the app-based audiometry assessment, unilateral hearing loss will be defined as at least one pure tone threshold greater than 25 decibels across at any one of the frequencies from 2,000 Hz- 8,000 Hz to align with the SIOP Boston guidelines, while bilateral hearing loss will be defined as a pure tone threshold \> 25 decibels in both ears at any one of the frequencies.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States