Evaluation of the Reliability of the Determination of MisMatch Repair Deficiency Status by Endoscopic Biopsies in Oesophagus and Gastric Adenocarcinoma.

NCT04774367 | Not Yet Recruiting

• 1 other identifier: APHP180152
• Study Type: interventional
• Target: 300
• Locations: 0 countries
• Sites: N/A

Brief Summary

Gastro-esophageal adenocarcinoma is one of the most common cancer in the world and the fourth most common cancer in France with more than 6,000 cases per year. For non-metastatic patients, a preoperative chemotherapy is recommended. As colorectal adenocarcinomas, gastroesophageal cancers (OGC) could be caused by a failure of DNA repair related to the loss of expression of one of the DNA repair proteins (MLH1, MSH2, PMS2, MSH6) (deficient MMR (dMMR)). The prevalence of tumors with dMMR is evaluated at 14% (Choi et al, 2014; Kim et al, 2015). This proportion reaches 25% among patients over 70 years old. Evidence suggests that patients with dMMR tumors do not benefit from neoadjuvant chemotherapy (Smyth et al, 2017), which may even have a negative impact, especially in elderly patients, and which should be discussed in this particular situation. The decision of neo-adjuvant chemotherapy must be taken very quickly after the endoscopic diagnosis. The investigators will evaluate the diagnostic performance of the determination of dMMR status by endoscopic biopsies of OGC. Moreover, there is no clear recommendation for the determination of dMMR status in OGC especially regarding the size of the forceps to use to ensure the quality of samples and the best molecular techniques for dMMR status determination. Methods In this prospective study, the investigators will include patients who will benefit from an upper endoscopy within 5 French hospital centers (Saint-Louis, Lariboisière, Beaujon, Bichat and Avicenne) linked to the NORDICAP network. If a suspect lesion of OGC is discovered during the gastroscopy, the endoscopist will perform at least 8 endoscopic biopsies, according to the recommendations, and by the mean of 2 kinds of forceps: standard biopsy forceps and a large capacity biopsy forceps. The clinical and follow-up data will be prospectively collected and will include demographics data, cancer stage, lymph node invasion, treatment history, recurrence and survival data. The investigators will assess MSI status by genotyping and MMR proteins expression by immunochemistry (IHC), performed, for each patient, on both biopsies and surgical tumor samples. Expected results This study will allow us to compare diagnostic performance of endoscopic biopsies to surgical samples for the assessment of dMMR status. Likewise, the investigators will compare the diagnostic performance of the two kinds of endoscopic forceps and of IHC and genotyping for the determination of dMMR phenotype. It will enable us to establish recommendations for the benefit of gastro-enterologists and pathologists.

Conditions

Gastro-oesophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Sensitivity (Se) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy

  The sensitivity will be evaluated by comparing the endocospic result with that obtained by the analysis of the specimen considered as the reference examination.

  at inclusion

• Specificity (Spe) of the determination of the dMMR status by the endoscopic biopsies performed at the time of the initial high endoscopy

  The specificity will be evaluated by comparing the endocospic result with that obtained by the analysis of the specimen considered as the reference examination.

  at inclusion

Secondary Outcomes (12)

• Positive likelihood ratios

  at inclusion

• Negative likelihood ratios

  at inclusion

• Sensitivity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )

  at inclusion

• Specificity of dMMR status diagnosis according to the forceps (standard and large capacity biopsy forceps )

  at inclusion

• Sensitivity of dMMR status diagnosis according to the techniques (immunohistochemistry and PCR)

  at inclusion

Study Arms (2)

Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

OTHER

Device: Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps

OTHER

Device: Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps

Interventions

Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps DEVICE

Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps DEVICE

Order of forceps : First standard biopsy forceps and second large capacity biopsy forceps

Order of forceps : First large capacity biopsy forceps and second standard biopsy forceps

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient having endoscopy biopsies in front of a suspicious lesion suggestive of gastroesophageal adenocarcinoma

You may not qualify if:

• Minor patient (\<18 years old)
• known pregnancy
• Major patient under tutorship or curatorship
• Contraindication to gastric biopsies

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Central Study Contacts

Thomas APARICIO

CONTACT

+33142499597; thomas.aparicio@aphp.fr

Matthieu Resche-Rigon

CONTACT

+33142499742; matthieu.resche-rigon@univ-paris-diderot.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 1, 2021
• Study Start: March 1, 2021
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2026
• Last Updated: March 3, 2021

Record last verified: 2021-02