Molecular Epidemiology of Pediatric Germ Cell Tumors

Germ Cell Tumor Clinical Trial

Official title:

Pediatric Germ Cell Tumors: Outcomes, Genomics and Epigenetics

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05564026
• Other study ID #: AEPI17N3
• Status: Recruiting
• Start date: April 12, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: December 2023
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1151
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2027
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Choriocarcinoma
• Embryonal Carcinoma
• Germ Cell Tumor
• Germinoma
• Late Effects
• Mixed Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Pediatric Germ Cell Tumor
• Teratoma
• Yolk Sac Tumor

Intervention

Other:
• Questionnaire Administration
Questionnaire provide to participant's about their health and quality of life since treatment
• Tumor Specimen Collection
Tumor DNA requested from the Biopathology Center
• Germline DNA Samples
Germline DNA specimens requested from the Biopathology Center or newly collected saliva

Procedure:
• Blood Sample Collection
Collection and storing of serum/plasma

Locations

Country	Name	City	State
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Children's Oncology Group

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ototoxicity	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.	Up to 5 years
Primary	Somatic Mutations	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.	Up to 5 years
Primary	Methylation	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.	Up to 5 years