Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas (NEONEC)

Phase II Study to Evaluate the Efficacy of 12-month Neoadjuvant Chemotherapy in Terms of Disease-free Survival in Patients With Localized Digestive Neuroendocrine Carcinomas

NEONEC is a single-phase, phase II study evaluating the efficacy of the 12-month neoadjuvant chemotherapy in patients with locally differentiated digestive NEC. The recommended chemotherapy is based on the current reference combination of platinum (cisplatin or carboplatin) and etoposide (VP16). For anorectal locations, radiochemotherapy is proposed to avoid the morbidity of conventional surgery.

The objective of the study is to improve relapse-free survival (RFS) in NEC patients treated with neoadjuvant chemotherapy followed by surgery or chemoradiotherapy.

In parallel, we will perform a prospective cohort study with patients whose diagnosis is made during surgery, who have not received neoadjuvant treatment, and who are offered an adjuvant treatment of the same type (combination of platinum and platinum salts and etoposide).

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Carcinoma; Digestive Cancer
• Intervention / Treatment: Drug: Neoadjuvant treatment; Drug: Adjuvant treatment

Detailed Description

A total of 48 patients is to be included in phase II and 30 patients in prospective cohort during the inclusion period of phase II.

Phase II study treatment:

Neoadjuvant chemotherapy: Administration of 4 cycles of chemotherapy (3 months) with platinum based chemotherapy (carboplatin or cisplatin, at the choice of the investigator) + etoposide.

Surgery or chemoradiotherapy depending on the tumor localization (the irradiation modalities and associated chemotherapy treatment will be left to the discretion of the referring radiotherapists according to current recommendations for each localization).

Prospective cohort:

• Surgery (prior to study entry)
• Adjuvant chemotherapy : Administration of 4 cycles of chemotherapy (3 months) with platinum based chemotherapy (carboplatin or cisplatin, at the choice of the investigator) + etoposide.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna PELLAT, MD; Phone Number: +33 (0) 1 49 28 23 45; Email: anna.pellat@aphp.fr
• Study Contact Backup: Name: Marie-Line GARCIA-LARNICOL; Email: marie-line.garcia-larnicol@gercor.com.fr

Study Locations

• France
  • Amiens, France
    • Recruiting
    • CHU Amiens - Hopital Sud
    • Principal Investigator: Vincent HAUTEFEUILLE, MD
    • Contact: Vincent HAUTEFEUILLE, MD; Phone Number: +33(0)322088854; Email: hautefeuille.vincent@chu-amiens.fr
  • Besançon, France
    • Recruiting
    • CHU Jean Minjoz
    • Contact: Fabien CALCAGNO, MD; Phone Number: +33(03)70632153; Email: fabien.calcagno@gmail.com
    • Principal Investigator: Fabien Calcagno, MD
  • Clichy, France
    • Recruiting
    • Hôpital Beaujon
    • Principal Investigator: Olivia HENTIC, MD
    • Contact: Olivia HENTIC, MD; Phone Number: + 33 (0)1 40 87 52 41; Email: olivia.hentic@aphp.fr
  • Dijon, France
    • Recruiting
    • CHU Dijon
    • Contact: Côme LEPAGE, MD; Phone Number: +33 (0)3 80 39 33 40; Email: come.lepage@u-bourgogne.fr
    • Principal Investigator: Côme LEPAGE, MD
  • Lyon, France
    • Not yet recruiting
    • Hôpital Edouard Herriot
    • Contact: Thomas WALTER, MD
    • Principal Investigator: Thomas WALTER, MD
  • Marseille, France
    • Not yet recruiting
    • Institut Paoli-Calmettes
    • Contact: Patricia NICCOLI, MD
    • Principal Investigator: Patricia NICCOLI, MD
  • Paris, France, 75012
    • Recruiting
    • Saint Antoine Hospital
    • Contact: Anna PELLAT; Phone Number: +33 (0) 1 49 28 23 45; Email: anna.pellat@aphp.fr
    • Contact: Pauline AFCHAIN; Phone Number: +33 (0) 1 49 28 23 45; Email: pauline.afchain@aphp.fr
  • Paris, France
    • Recruiting
    • Hôpital Saint Antoine
    • Contact: Pauline AFCHAIN, MD; Phone Number: +33 (0)1 49 28 23 29; Email: pauline.afchain@aphp.fr
    • Principal Investigator: Pauline AFCHAIN, MD
  • Paris, France
    • Not yet recruiting
    • Hôpital Cochin
    • Contact: Romain CORIAT, MD
    • Principal Investigator: Romain CORIAT, MD
  • Paris, France
    • Not yet recruiting
    • Groupe Hospitalier Diaconesses Croix Saint Simon
    • Contact: Olivier DUBREUIL, MD
    • Principal Investigator: Olivier DUBREUIL, MD
  • Pessac, France
    • Recruiting
    • Hôpital Haut Lévêque CHU Bordeaux
    • Principal Investigator: Denis SMITH, MD
    • Contact: Denis SMITH, MD; Phone Number: + 33 (0)5 57 65 64 39; Email: denis.smith@chu-bordeaux.fr
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Contact: David TOUGERON, MD; Phone Number: +33(05)49443751; Email: David.TOUGERON@chu-poitiers.fr
    • Principal Investigator: David TOUGERON, MD
  • Toulouse, France
    • Recruiting
    • CHU Toulouse
    • Contact: Rosine GUIMBAUD, MD; Phone Number: +33 (0)561779649; Email: guimbaud.r@chu-toulouse.fr
    • Principal Investigator: Rosine Guimbaud, MD
  • Villejuif, France
    • Not yet recruiting
    • Institut Gustave Roussy
    • Contact: Michel DUCREUX, MD
    • Principal Investigator: Michel DUCREUX, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Phase II

1. Histologically proven digestive CNE, (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. Written informed consent obtained from the patient, willing and able to comply with the protocol, 7. Registration in a National Health Care System (Protection Universelle Maladie [PUMa] included), 8. 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.

Prospective cohort

1. Patients with localized digestive CNE histologically proven on the operative specimen (the WHO 2017 classification: poorly differentiated and Ki 67> 20%),
2. Localized, without metastasis on computed tomography [CT], thoracoabdominopelvic CT scan [TAP] RECIST 1.1, and/or locoregional lymph node involvement,
3. Age ≥ 18 years,
4. Written informed consent obtained from the patient, willing and able to comply with the protocol,
5. Registration in a National Health Care System (PUMa - Protection Universelle Maladie included),
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 methods during the study (if applicable) during the period of treatment and during 6 months from the last treatment administration.

Exclusion Criteria:

Phase II

1. Well-differentiated NEC, whatever the grade,
2. Metastatic disease,
3. Cancer of unknown primary
4. Organ failure that does not allow chemotherapy treatment,
5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
6. Tumor with a mixed component (component accounts for ≥ 30%),
7. Patient impossible to follow-up,
8. Other than platinum-etoposide chemotherapy administrated,
9. Tutelage or guardianship or patient protected by law

Prospective cohort

1. Well-differentiated NEC, whatever the grade,
2. Metastatic disease,
3. Cancer of unknown primary
4. Organ failure that does not allow chemotherapy treatment,
5. Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
6. Tumor with a mixed component (component accounts for ≥ 30%),
7. Patient impossible to follow-up,
8. Other than platinum-etoposide chemotherapy administrated,
9. Tutelage or guardianship or patient protected by law.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase II; Prospective, open, multi center, one-arm, national phase II study evaluating the benefits in terms of disease-free survival (DFS) at 12 months after the administration of neoadjuvant treatment in patients with localized digestive neuroendocrine carcinomas	Drug: Neoadjuvant treatment; 4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide followed by surgery or chemoradiotherapy; Other Names: cisplatin / cisplatinum; etoposide / vepesid; carbopatin / paraplatin
Active Comparator: Prospective cohort; Evaluation of DFS at 12 months in patients who underwent surgery and received adjuvant chemotherapy	Drug: Adjuvant treatment; Surgery (before study entry) followed by 4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide; Other Names: cisplatin / cisplatinum; etoposide / vepesid; carbopatin / paraplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS) - phase II	Interval between the date of the start of treatment (chemotherapy) and the date of first relapse or death (all causes). Relapse is defined according to RECIST version 1.1 criteria.	At 12 months
Relapse-free survival (RFS) - prospective cohort	Interval between the date of the start of treatment (chemotherapy) and the date of first relapse or death (all causes). Relapse is defined according to RECIST version 1.1 criteria.	At 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient in response in pre-operative or prior radiochemotherapy (if applicable) - Phase II	according to RECIST 1.1	At 3 months after the beginning of treatment (up to 36 months)
Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II	Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II	Up to 39 months
Number of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if applicable) - Phase II	Number of patients operated after neoadjuvant chemotherapy or receiving	Up to 39 months
Overall survival (OS) - Phase II	Overall survival (OS) is defined as the time from study enrollment to death (from any cause) or to the last date the patients was known to be alive.	up to 48 months
Overall survival (OS) - Prospective cohort	Overall survival (OS) is defined as the time from study enrollment to death (from any cause) or to the last date the patients was known to be alive.	Up to 48 months
Number of participants with treatment-related adverse events grade 3-4 as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 - Phase II	Patients will be assessed for AEs throughout the study at every visit during treatment. Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs. Institute Common Terminology Criteria for Adverse Toxicity Study (NCI-CTCAE) version 5.0	Up to 43 months
Number of participants with treatment-related adverse events grade 3-4 as assessed by National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE] v5.0 - Prospective cohort	Patients will be assessed for AEs throughout the study at every visit during treatment. Investigators using the NCI-CTCAE version 5.0 will grade the severity of AEs. Institute Common Terminology Criteria for Adverse Toxicity Study (NCI-CTCAE) version 5.0	Up to 43 months

Collaborators and Investigators

• Sponsor: GERCOR - Multidisciplinary Oncology Cooperative Group
• Collaborators: Fondation ARCAD
• Investigators: Principal Investigator: Anna PELLAT, Saint-Antoine Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Adjuvant treatment; Neoadjuvant treatment
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Carcinoma; Carcinoma, Neuroendocrine; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Etoposide; Carboplatin; Cisplatin; Etoposide phosphate
• Other Study ID Numbers: NEONEC D19-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No