Evaluate the efficacy of 12-month neoadjuvant chemotherapy in terms of disease-free survival in patients with localized digestive neuroendocrine carcinomas

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Association Gercor

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-01-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2024-515603-19-01

EudraCT number

2019-004096-39

ClinicalTrials.gov

NCT04268121

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others

Phase II
Demonstrate a benefit in terms of relapse-free survival (RFS) at 12 months after the start of administration of neoadjuvant therapy in patients with resectable localized digestive CNE.

Secondary objectives 9

1. To assess the response rate of preoperative neoadjuvant treatment regimen (or pre-radiochemotherapy)
2. Evaluate the number of progressive patients who no longer have an indication for surgery or radiochemotherapy
3. Evaluate the number of patients operated after neoadjuvant treatment or receiving radiochemotherapy if applicable
4. To assess the histological response rate (tumor regression grade [TRG]) in operated patients
5. To assess the pTNM stage on the surgical resection piece
6. To assess OS
7. To assess the feasibility of the therapeutic regimen of neoadjuvant treatment
8. To assess the toxicity of neoadjuvant therapy and post -surgery
9. Analysis of tumor tissue and ctDNA levels

Conditions and MedDRA coding

Localized digestive Neuroendocrine Carcinomas

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Histologically proven digestive CNE on biopsy, (the WHO 2017 classification: poorly differentiated and Ki 67 > 20%),
2. 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),
3. Positron emission tomography (PET) and CT for lymph node status and elimination of secondary visceral and/or bone disorders,
4. Resectable tumor, according to the consensus decision made during local multidisciplinary surgical consultation meeting,
5. Age ≥ 18 years
6. 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 11

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 12-month RFS (relapse-free survival without locale or metastatic relapse and without death) for NEC patients receiving neoadjuvant chemotherapy
2. 12-month RFS in CNE patients undergoing surgery

Secondary endpoints 9

1. Pre-operative response rate or prior radiochemotherapy response rate according to RECIST 1.1,
2. Rate of patients who do not benefit from surgery or radiochemotherapy
3. Rate of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if appropriate),
4. Degree of histological response (tumor regression grade [TRG]),
5. Overall survival (OS),
6. Description and the treatment regimens feasibility,
7. 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
8. 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.
9. ctDNA analysis: samples at Baseline and before surgery

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Association Gercor

Sponsor organisation

Association Gercor

Address

151 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75011

Country

France

Scientific contact point

Organisation

Association Gercor

Contact name

Marie-line GARCIA LARNICOL

Public contact point

Organisation

Association Gercor

Contact name

Viviane MABOPDA

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications