Back to resultsEfficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas (NEONEC)
Primary Purpose
Neuroendocrine Carcinoma, Digestive Cancer
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Neoadjuvant treatment
Adjuvant treatment
Sponsored by
About this trial
This is an interventional treatment trial for Neuroendocrine Carcinoma focused on measuring Neoadjuvant treatment, Adjuvant treatment
Eligibility Criteria
Inclusion Criteria:
Phase II
- Histologically proven digestive CNE, (the WHO 2017 classification: poorly differentiated and Ki 67 > 20%),
- 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),
- 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
- Patients with localized digestive CNE histologically proven on the operative specimen (the WHO 2017 classification: poorly differentiated and Ki 67> 20%),
- Localized, without metastasis on computed tomography [CT], thoracoabdominopelvic CT scan [TAP] RECIST 1.1, and/or locoregional lymph node involvement,
- Age ≥ 18 years,
- Written informed consent obtained from the patient, willing and able to comply with the protocol,
- Registration in a National Health Care System (PUMa - Protection Universelle Maladie included),
- 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
- Well-differentiated NEC, whatever the grade,
- Metastatic disease,
- Cancer of unknown primary
- Organ failure that does not allow chemotherapy treatment,
- Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
- Tumor with a mixed component (component accounts for ≥ 30%),
- Patient impossible to follow-up,
- Other than platinum-etoposide chemotherapy administrated,
- Tutelage or guardianship or patient protected by law
Prospective cohort
- Well-differentiated NEC, whatever the grade,
- Metastatic disease,
- Cancer of unknown primary
- Organ failure that does not allow chemotherapy treatment,
- Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
- Tumor with a mixed component (component accounts for ≥ 30%),
- Patient impossible to follow-up,
- Other than platinum-etoposide chemotherapy administrated,
- Tutelage or guardianship or patient protected by law.
Sites / Locations
- CHU Amiens - Hôpital SudRecruiting
- CHU Jean MinjozRecruiting
- Hôpital BeaujonRecruiting
- CHU DijonRecruiting
- Hôpital Edouard Herriot
- Institut Paoli-Calmettes
- Saint Antoine HospitalRecruiting
- Groupe Hospitalier Diaconesses Croix Saint Simon
- Hôpital Cochin
- Hôpital Saint AntoineRecruiting
- Hôpital Haut Lévêque CHU BordeauxRecruiting
- CHU PoitiersRecruiting
- CHU ToulouseRecruiting
- Institut Gustave Roussy
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Phase II
Prospective cohort
Arm Description
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
Evaluation of DFS at 12 months in patients who underwent surgery and received adjuvant chemotherapy
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Number of patient in response in pre-operative or prior radiochemotherapy (if applicable) - Phase II
according to RECIST 1.1
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
Number of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if applicable) - Phase II
Number of patients operated after neoadjuvant chemotherapy or receiving
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.
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.
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
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
Full Information
NCT ID
NCT04268121
First Posted
February 11, 2020
Last Updated
June 28, 2023
Sponsor
GERCOR - Multidisciplinary Oncology Cooperative Group
Collaborators
Fondation ARCAD
1. Study Identification
Unique Protocol Identification Number
NCT04268121
Brief Title
Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas
Acronym
NEONEC
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 5, 2021 (Actual)
Primary Completion Date
January 2034 (Anticipated)
Study Completion Date
June 2034 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GERCOR - Multidisciplinary Oncology Cooperative Group
Collaborators
Fondation ARCAD
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroendocrine Carcinoma, Digestive Cancer
Keywords
Neoadjuvant treatment, Adjuvant treatment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Phase II and prospective cohort
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
78 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase II
Arm Type
Experimental
Arm Description
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
Arm Title
Prospective cohort
Arm Type
Active Comparator
Arm Description
Evaluation of DFS at 12 months in patients who underwent surgery and received adjuvant chemotherapy
Intervention Type
Drug
Intervention Name(s)
Neoadjuvant treatment
Other Intervention Name(s)
cisplatin / cisplatinum, etoposide / vepesid, carbopatin / paraplatin
Intervention Description
4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide followed by surgery or chemoradiotherapy
Intervention Type
Drug
Intervention Name(s)
Adjuvant treatment
Other Intervention Name(s)
cisplatin / cisplatinum, etoposide / vepesid, carbopatin / paraplatin
Intervention Description
Surgery (before study entry) followed by 4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide
Primary Outcome Measure Information:
Title
Relapse-free survival (RFS) - phase II
Description
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.
Time Frame
At 12 months
Title
Relapse-free survival (RFS) - prospective cohort
Description
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.
Time Frame
At 12 months
Secondary Outcome Measure Information:
Title
Number of patient in response in pre-operative or prior radiochemotherapy (if applicable) - Phase II
Description
according to RECIST 1.1
Time Frame
At 3 months after the beginning of treatment (up to 36 months)
Title
Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II
Description
Number of patients who do not benefit from surgery or radiochemotherapy (if applicable) - Phase II
Time Frame
Up to 39 months
Title
Number of patients operated after neoadjuvant chemotherapy or receiving radiochemotherapy (if applicable) - Phase II
Description
Number of patients operated after neoadjuvant chemotherapy or receiving
Time Frame
Up to 39 months
Title
Overall survival (OS) - Phase II
Description
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.
Time Frame
up to 48 months
Title
Overall survival (OS) - Prospective cohort
Description
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.
Time Frame
Up to 48 months
Title
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
Description
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
Time Frame
Up to 43 months
Title
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
Description
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
Time Frame
Up to 43 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Phase II
Histologically proven digestive CNE, (the WHO 2017 classification: poorly differentiated and Ki 67 > 20%),
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),
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
Patients with localized digestive CNE histologically proven on the operative specimen (the WHO 2017 classification: poorly differentiated and Ki 67> 20%),
Localized, without metastasis on computed tomography [CT], thoracoabdominopelvic CT scan [TAP] RECIST 1.1, and/or locoregional lymph node involvement,
Age ≥ 18 years,
Written informed consent obtained from the patient, willing and able to comply with the protocol,
Registration in a National Health Care System (PUMa - Protection Universelle Maladie included),
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
Well-differentiated NEC, whatever the grade,
Metastatic disease,
Cancer of unknown primary
Organ failure that does not allow chemotherapy treatment,
Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
Tumor with a mixed component (component accounts for ≥ 30%),
Patient impossible to follow-up,
Other than platinum-etoposide chemotherapy administrated,
Tutelage or guardianship or patient protected by law
Prospective cohort
Well-differentiated NEC, whatever the grade,
Metastatic disease,
Cancer of unknown primary
Organ failure that does not allow chemotherapy treatment,
Previous malignancy within 5 years prior to the study except for cutaneous basal cell carcinoma and uterine cancer in situ
Tumor with a mixed component (component accounts for ≥ 30%),
Patient impossible to follow-up,
Other than platinum-etoposide chemotherapy administrated,
Tutelage or guardianship or patient protected by law.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anna PELLAT, MD
Phone
+33 (0) 1 49 28 23 45
Email
anna.pellat@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Marie-Line GARCIA-LARNICOL
Email
marie-line.garcia-larnicol@gercor.com.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna PELLAT
Organizational Affiliation
Saint-Antoine Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Amiens - Hôpital Sud
City
Amiens
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent HAUTEFEUILLE, MD
Phone
+33(0)322088854
Email
hautefeuille.vincent@chu-amiens.fr
First Name & Middle Initial & Last Name & Degree
Vincent HAUTEFEUILLE, MD
Facility Name
CHU Jean Minjoz
City
Besançon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fabien CALCAGNO, MD
Phone
+33(03)70632153
Email
fabien.calcagno@gmail.com
First Name & Middle Initial & Last Name & Degree
Fabien CALCAGNO, MD
Facility Name
Hôpital Beaujon
City
Clichy
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivia HENTIC, MD
Phone
+ 33 (0)1 40 87 52 41
Email
olivia.hentic@aphp.fr
First Name & Middle Initial & Last Name & Degree
Olivia HENTIC, MD
Facility Name
CHU Dijon
City
Dijon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Côme LEPAGE, MD
Phone
+33 (0)3 80 39 33 40
Email
come.lepage@u-bourgogne.fr
First Name & Middle Initial & Last Name & Degree
Côme LEPAGE, MD
Facility Name
Hôpital Edouard Herriot
City
Lyon
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas WALTER, MD
First Name & Middle Initial & Last Name & Degree
Thomas WALTER, MD
Facility Name
Institut Paoli-Calmettes
City
Marseille
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia NICCOLI, MD
First Name & Middle Initial & Last Name & Degree
Patricia NICCOLI, MD
Facility Name
Saint Antoine Hospital
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anna PELLAT
Phone
+33 (0) 1 49 28 23 45
Email
anna.pellat@aphp.fr
First Name & Middle Initial & Last Name & Degree
Pauline AFCHAIN
Phone
+33 (0) 1 49 28 23 45
Email
pauline.afchain@aphp.fr
Facility Name
Groupe Hospitalier Diaconesses Croix Saint Simon
City
Paris
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivier DUBREUIL, MD
First Name & Middle Initial & Last Name & Degree
Olivier DUBREUIL, MD
Facility Name
Hôpital Cochin
City
Paris
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Romain CORIAT, md
First Name & Middle Initial & Last Name & Degree
Romain CORIAT, MD
Facility Name
Hôpital Saint Antoine
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pauline AFCHAIN, MD
Phone
+33 (0)1 49 28 23 29
Email
pauline.afchain@aphp.fr
First Name & Middle Initial & Last Name & Degree
Pauline AFCHAIN, MD
Facility Name
Hôpital Haut Lévêque CHU Bordeaux
City
Pessac
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denis SMITH, MD
Phone
+ 33 (0)5 57 65 64 39
Email
denis.smith@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Denis SMITH, MD
Facility Name
CHU Poitiers
City
Poitiers
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David TOUGERON, MD
Phone
+33(05)49443751
Email
David.TOUGERON@chu-poitiers.fr
First Name & Middle Initial & Last Name & Degree
David TOUGERON, MD
Facility Name
CHU Toulouse
City
Toulouse
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosine GUIMBAUD, MD
Phone
+33 (0)561779649
Email
guimbaud.r@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Rosine GUIMBAUD, MD
Facility Name
Institut Gustave Roussy
City
Villejuif
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel DUCREUX, MD
First Name & Middle Initial & Last Name & Degree
Michel DUCREUX, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy of Neoadjuvant Chemotherapy in Terms of DFS in Patients With Localized Digestive Neuroendocrine Carcinomas
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