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%),"}
• {"criterion_text":"- 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),"}
• {"criterion_text":"- Positron emission tomography (PET) and CT for lymph node status and elimination of secondary visceral and/or bone disorders,"}
• {"criterion_text":"- Resectable tumor, according to the consensus decision made during local multidisciplinary surgical consultation meeting,"}
• {"criterion_text":"- Age ≥ 18 years"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Metastatic disease"}
• {"criterion_text":"- Cancer of unknown primary"}
• {"criterion_text":"- Organ failure that does not allow chemotherapy treatment"}
• {"criterion_text":"- History of invasive malignacy disease within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ"}
• {"criterion_text":"- Tumor with a mixed component (component accounts for ≥ 30%),"}
• {"criterion_text":"- Other than platinum-etoposide chemotherapy administrated,"}

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 without local or metastatic relapse and without death measured at 12 months after start of neoadjuvant chemotherapy (as stated)."}
• {"endpoint_text":"- 12-month RFS in CNE patients undergoing surgery","definition_or_measurement_approach":"Recurrence-free survival at 12 months after surgery (as stated)."}

Secondary endpoints

• {"endpoint_text":"- Pre-operative response rate or prior radiochemotherapy response rate according to RECIST 1.1,","definition_or_measurement_approach":"Response assessed pre-operatively according to RECIST v1.1."}
• {"endpoint_text":"- Rate of patients who do not benefit from surgery or radiochemotherapy","definition_or_measurement_approach":"Rate of progressive patients who no longer have an indication for surgery or radiochemotherapy (as stated)."}
• {"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 if applicable (as stated)."}
• {"endpoint_text":"- Degree of histological response (tumor regression grade [TRG]),","definition_or_measurement_approach":"Histological tumor regression grade assessed on surgical specimen."}
• {"endpoint_text":"- Overall survival (OS),","definition_or_measurement_approach":"Overall survival measured from start of treatment (as stated)."}
• {"endpoint_text":"- Description and the treatment regimens feasibility,","definition_or_measurement_approach":"Feasibility assessment of therapeutic regimen (as stated)."}
• {"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."}
• {"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 for listed markers on tumor tissue; MSI determination; molecular panel analysis for listed genes/translocations (as stated)."}
• {"endpoint_text":"- ctDNA analysis: samples at Baseline and before surgery","definition_or_measurement_approach":"Circulating tumor DNA analysis at baseline (or C1D1) and pre-operatively (as stated)."}

France

Earliest CTIS Part Ii Submission Date

15-07-2024

Latest Decision Or Authorization Date

13-08-2024

Processing Time Days

29

Number Of Sites

14

Number Of Participants

78

Primary sponsor

Full Name

Association Gercor

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France