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

Neuroendocrine Carcinoma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04268121
• Other study ID #: NEONEC D19-01
• Status: Recruiting
• Phase: Phase 2
• Start date: January 5, 2021
• Est. completion date: June 2034

Study information

• Verified date: June 2023
• Source: GERCOR - Multidisciplinary Oncology Cooperative Group
• Contact: Anna PELLAT, MD
• Phone: +33 (0) 1 49 28 23 45
• Email: anna.pellat[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: June 2034
• Est. primary completion date: January 2034
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Neuroendocrine
• Digestive Cancer
• Neuroendocrine Carcinoma

Intervention

Drug:
• Neoadjuvant treatment
4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide followed by surgery or chemoradiotherapy
• Adjuvant treatment
Surgery (before study entry) followed by 4 cycles of platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide

Locations

Country	Name	City	State
France	CHU Amiens - Hôpital Sud	Amiens
France	CHU Jean Minjoz	Besançon
France	Hôpital Beaujon	Clichy
France	CHU Dijon	Dijon
France	Hôpital Edouard Herriot	Lyon
France	Institut Paoli-Calmettes	Marseille
France	Groupe Hospitalier Diaconesses Croix Saint Simon	Paris
France	Hôpital Cochin	Paris
France	Hôpital Saint Antoine	Paris
France	Saint Antoine Hospital	Paris
France	Hôpital Haut Lévêque CHU Bordeaux	Pessac
France	CHU Poitiers	Poitiers
France	CHU Toulouse	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
GERCOR - Multidisciplinary Oncology Cooperative Group	Fondation ARCAD

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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