ETOPOSIDE for Localized digestive neuroendocrine carcinoma

Inclusion criteria

• {"criterion_text":"- Histologically proven digestive CNE on biopsy, (the WHO 2017 classification: poorly differentiated and Ki 67 > 20%),\n- Patients with localized CNE, without metastasis (computed tomography [CT], thoraco-abdominopelvic CT scan [TAP] according to RECIST 1.1; examinations performed no later than 21 days before starting the study treatment, possible locoregional lymph node involvement defined according to the TNM classification),\n- Positron emission tomography (PET) and CT for lymph node status and elimination of secondary visceral and/or bone disorders,\n- Resectable tumor, according to the consensus decision made during local multidisciplinary surgical consultation meeting,\n- Age ≥ 18 years\n- For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study treatment. Men and women are required to use a reliable and adequate birth control during the study (if applicable) during the period of treatment and during 6 months from the last treatment administration"}

Exclusion criteria

• {"criterion_text":"- Well-differentiated NEC, whatever the grade\n- Different chemotherapy regimen administered\n- \"More than one cycle of chemotherapy administered before inclusion in the study.\n- Patient under guardianship, legal protection, or judicial custody\n- Metastatic disease\n- Cancer of unknown primary\n- Organ failure that does not allow chemotherapy treatment\n- History of invasive malignacy disease within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ\n- Tumor with a mixed component (component accounts for ≥ 30%),\n- More than one cycle of chemotherapy administered prior to inclusion in the study\n- Follow-up impossible"}

Primary endpoints

• {"endpoint_text":"- 12-month RFS (relapse-free survival without locale or metastatic relapse and without death) for NEC patients receiving neoadjuvant chemotherapy","definition_or_measurement_approach":"Relapse-free survival at 12 months after start of neoadjuvant therapy, defined as absence of local or metastatic relapse and absence of death."}
• {"endpoint_text":"- 12-month RFS in CNE patients undergoing surgery","definition_or_measurement_approach":"Relapse-free survival at 12 months after surgery in CNE patients who underwent surgery."}

Secondary endpoints

• {"endpoint_text":"- Pre-operative response rate or prior radiochemotherapy response rate according to RECIST 1.1,","definition_or_measurement_approach":"Response assessed according to RECIST v1.1."}
• {"endpoint_text":"- Rate of patients who do not benefit from surgery or radiochemotherapy","definition_or_measurement_approach":"Proportion of patients who progress and no longer have indication for surgery or radiochemotherapy."}
• {"endpoint_text":"- Rate of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if appropriate),","definition_or_measurement_approach":"Proportion of patients who undergo surgery after neoadjuvant chemotherapy or who receive radiochemotherapy when appropriate."}
• {"endpoint_text":"- Degree of histological response (tumor regression grade [TRG]),","definition_or_measurement_approach":"Assessment of histological tumor regression grade (TRG) on surgical specimen."}
• {"endpoint_text":"- Overall survival (OS),","definition_or_measurement_approach":"Overall survival measured from inclusion/start of treatment to death from any cause."}
• {"endpoint_text":"- Description and the treatment regimens feasibility,","definition_or_measurement_approach":"Descriptive assessment of feasibility of the neoadjuvant treatment regimen (e.g., treatment completion rates, delays, modifications)."}
• {"endpoint_text":"- Collection of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Toxicity Study (NCI CTCAE) version 5.0 for neoadjuvant treatment and post surgery","definition_or_measurement_approach":"Adverse events collected and graded using NCI CTCAE v5.0 for neoadjuvant and post-surgery periods."}
• {"endpoint_text":"- Biomarkers analysis – immunohistochemical analysis of the most specific markers of NEC (CD56, chromogranin A/B, synaptophysin, TTF1, DLL3, ASCL1, NOTCH, p53, p16 and Rb, possible best response to platinum-etoposide-based chemotherapy - if the expression of Rb is lost), and determination of the microsatellite instability (MSI) status. Comprehensive analysis of a panel of genes especially including RAS, RAF, HER2 or anti-EGFR, AKT, Pi3KCA, MET, and ALK-EML4 translocation will be also performed.","definition_or_measurement_approach":"Immunohistochemistry on tumor blocks for listed markers; MSI determination; molecular panel sequencing for listed genes/alterations."}
• {"endpoint_text":"- ctDNA analysis: samples at Baseline and before surgery","definition_or_measurement_approach":"Circulating tumor DNA analysis performed at baseline (or C1D1) and pre-operatively."}

France

Earliest CTIS Part Ii Submission Date

22-01-2025

Latest Decision Or Authorization Date

14-10-2025

Processing Time Days

265

Number Of Sites

16

Number Of Participants

78

Primary sponsor

Full Name

Association Gercor

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France