Fertility Preservation in Children With Solid Tumors: Detection of Residual Disease by a Sensitive Method

NCT07141862 | Recruiting

• 1 other identifier: 2025_BRUGNON_PREFERPUBER
• Study Type: observational
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

In prepubertal patients, cryopreservation of ovarian or testicular tissue is currently the only available method for fertility preservation prior to gonadotoxic cancer treatments. However, this approach carries the risk of reintroducing malignant cells upon autotransplantation, particularly in cases of metastatic cancers such as neuroblastoma and Ewing sarcoma. Therefore, it is crucial to employ highly sensitive techniques to detect minimal residual disease (MRD) in preserved gonadal tissues. This study aims to identify the most effective detection method by comparing the sensitivity and specificity of reverse transcription quantitative PCR (RT-qPCR) and droplet digital PCR (ddPCR) in identifying MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues from patients treated for these malignancies during infancy.

Conditions

Neuroblastoma; Ewing Sarcoma

Outcome Measures

Primary Outcomes (1)

• Validation of residual disease detection of neuroblastoma and Ewing sarcoma by ddPCR in ovarian and testicular tissues.

  Detection of the copy number of specific tumor genes: PHOX2B for neuroblastoma and EWSR1-FLI1 for Ewing sarcoma in ovarian and testicular tissues using ddPCR. Residual disease will be detected in ovarian and testicular tissues contaminated with increasing quantities of tumor cells (0, 5, 10, 20, and 100 tumor cells) from neuroblastoma (IMR-32) and Ewing sarcoma (RD-ES), as well as in ovarian and testicular tissues from prepubertal patients diagnosed and treated for neuroblastoma and Ewing sarcoma during infancy.

  From 02-2025 to 02-2026 for analysis of neuroblastoma; from 02-2026 to 12-2027 for analysis of Ewing sarcoma.

Secondary Outcomes (2)

• Evaluation of the specificity and sensitivity of RT-qPCR and ddPCR for detecting residual disease of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues.

  From 02-2025 to 02-2026 for analysis of neuroblastoma; from 02-2026 to 12-2027 for analysis of Ewing sarcoma.

• Evaluation of the impact of ovarian tissue freezing protocols on RNA Quantity and Purity

  From 02-2025 to 02-2026 for analysis of neuroblastoma; from 02-2026 to 12-2027 for analysis of Ewing sarcoma

Study Arms (2)

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using RT-qPCR

First, the detection of minimal residual disease of neuroblastoma and Ewing sarcoma will be performed on an in vitro model that mimics the metastatic dissemination of these two solid tumors. Ovarian and testicular tissues will be contaminated with increasing quantities of tumor cells (0, 5, 10, 20, and 100 tumor cells) from neuroblastoma (IMR-32) and Ewing sarcoma (RD-ES). Then, the detection of MRD will be carried out on ovarian and testicular tissues from prepubertal patients diagnosed and treated for neuroblastoma and Ewing sarcoma during infancy. To detect this MRD in both models, the investigators will perform RNA extraction using TRIzol reagent, followed by reverse transcription and RT-qPCR to detect the specific tumor genes: PHOX2B for neuroblastoma and EWSR1-FLI1 for Ewing sarcoma.

Diagnostic Test: RT-qPCR

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using ddPCR.

First, the detection of MRD of neuroblastoma and Ewing sarcoma will be performed on an in vitro model that mimics the metastatic dissemination of these two solid tumors. Ovarian and testicular tissues will be contaminated with increasing quantities of tumor cells (0, 5, 10, 20, and 100 tumor cells) from neuroblastoma (IMR-32) and Ewing sarcoma (RD-ES). Then, the detection of MRD will be carried out on ovarian and testicular tissues from prepubertal patients diagnosed and treated for neuroblastoma and Ewing sarcoma during infancy. To detect this MRD in both models, the investigators will perform RNA extraction using TRIzol reagent, followed by reverse transcription and ddPCR to detect the specific tumor genes: PHOX2B for neuroblastoma and EWSR1-FLI1 for Ewing sarcoma.

Diagnostic Test: ddPCR

Interventions

RT-qPCR DIAGNOSTIC_TEST

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using RT-qPCR

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using RT-qPCR

ddPCR DIAGNOSTIC_TEST

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using ddPCR

Detection of MRD of neuroblastoma and Ewing sarcoma in ovarian and testicular tissues using ddPCR.

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Residual disease detection will be conducted on ovarian and testicular tissues collected from prepubertal patients diagnosed and treated for neuroblastoma or Ewing sarcoma during infancy

You may qualify if:

• Women of any age diagnosed with a benign cyst requiring laparoscopy may be included.
• Men of any age diagnosed with a non-obstructive azoospermia may be included.
• Prepubertal girls and boys diagnosed with neuroblastoma or Ewing sarcoma during infancy may be included.
• Capable of providing written informed consent to participate in the research study
• Affiliated with a social welfare service.
• For prepubertal patients, written informed consent to participate in the research study must be provided by their parents or legal guardians.

You may not qualify if:

• None

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• University Hospital, Rouen: collaborator

Study Sites (1)

University hospital

Clermont-Ferrand, Auvergne, 63000, France

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Sarcoma, Ewing

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Study Officials

• Florence BRUGNON, MD, PhD, HDR

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lise Laclautre

CONTACT

04 73 75 11 95; drci@chu-clermontferrand.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2025
• First Posted: August 26, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 3, 2025

Record last verified: 2025-07

Locations

FR (1)