First Line Chemotherapy for Metastatic Gastro Entero Pancreatic Neuroendocrine Carcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Dijon

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Oct 2024 → ongoing

Decision date (initial)

2024-10-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515300-39-00

EudraCT number

2019-001013-16

ClinicalTrials.gov

NCT04325425

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenetic, Efficacy, Safety, Therapy

To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.

Secondary objectives 9

1. PFS according to the centralized review (RECIST v1.1 criteria)
2. Best objective response rate (ORR)
3. Median overall survival (OS)
4. Safety according to NCI CTC V4.0
5. Dose-reductions
6. Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L
7. To establish a molecular profile within 2 months after tumor sample submission for each patient enrolled in the study and to provide a molecular tumor board report to the treating physician.
8. Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype
9. Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…)

Conditions and MedDRA coding

METASTATIC GRADE 3 POORLY DIFFERENTIATED NEUROENDOCRINE CARCINOMA OF GASTRO ENTERO PANCREATIC AND UNKNOWN PRIMARY

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Grade 3 neuroendocrine carcinoma (Ki67>20%) or high grade MiNEN with a grade 3 poorly differentiated neuroendocrine carcinoma
2. Primary gastro-entero-pancreatic or unknown primary
3. Small cell or large cell or non-small cell or non- typeable neuroendocrine carcinoma
4. Metastatic disease
5. ECOG performance status ≤ 1
6. First line treatment for metastatic disease. No prior chemotherapy or systemic therapy for management of metastatic disease or primary tumor
7. At least one measurable lesion as assessed by CT-scan or MRI according to RECIST 1.1 guidelines
8. Available tumor block
9. ANC ≥ 1.5x109/l, platelet ≥ 100x109/l and haemoglobin > 8 g/dl
10. Total bilirubin ≤ 1.5N, AST ≤ 2.5N, ALT≤ 2.5N or AST and ALT ≤ 5N in case of liver metastasis.
11. Age ≥ 18 years
12. Signed and dated informed consent, and willing and able to comply with protocol requirements.
13. Women of childbearing potential, as well as men (who have sexual relations with women of childbearing potential) must agree to use an effective method of contraception throughout this study and during the 15 months following administration of the last dose of the study medicinal product
14. Patient who is a beneficiary of the Social security system

Exclusion criteria 20

1. Grade 3 well differentiated neuroendocrine tumor according to WHO 2017 classification
2. Severe renal impairment (creatinine clearance less than 30 mL/min, Cockroft and Gault)
3. ECOG performance status > 1
4. Partial or complete Dihydropyrimidine Dehydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
5. Known Gilbert's syndrome
6. Pre-existing permanent neuropathy (NCI CTC V4.0 grade ≥2)
7. Previously treated by chemotherapy or targeted therapy
8. Symptomatic brain metastases patient with asymptomatic brain metastases or under stable corticosteroid doses for at least 2 weeks before randomization can be included.
9. Combination with sorivudine and others analogues of dihydropyrimidine dehydrogenase)
10. Treatment with St John's Wort (Hypericum perforatum)
11. Pregnant women or breastfeeding mother
12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C
13. History of prior malignancy in the three yars before randomization, except for cured non-melanoma skin cancer and cured in situ cervical carcinoma.
14. Active or suspected acute or chronic uncontrolled disease that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study
15. vaccinations (live vaccine) within 30 days prior to start of study drugs
16. Patient under guardianship and/or deprived of his/her freedom
17. QTc interval > 450 msec for male and > 470 msec for female at EKC.
18. K+ < LLN, Mg²+ < LLN, Ca²+ < LLN
19. History or know hypersensitivity to any of the study chemotherapy agents, or their excipients.
20. Patient already participating in another clinical trial who is currently being treated or whose treatment was completed less than four weeks prior to inclusion.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.

Secondary endpoints 9

1. PFS according to the centralized review (RECIST v1.1 criteria)
2. Best objective response rate (ORR)
3. Median overall survival (OS)
4. Safety according to NCI CTC V4.0
5. Dose-reductions
6. Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L
7. To establish a molecular profile within 2 months after tumor sample submission for each patient enrolled in the study anmolecular tumor board report to the treating physician.d to provide a
8. Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype
9. Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…)

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Dijon

Sponsor organisation

Centre Hospitalier Universitaire De Dijon

Address

1 Boulevard Jeanne D Arc, Bp 77908 Bp 77908

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

coordinator

Public contact point

Organisation

Centre Hospitalier Universitaire De Dijon

Contact name

coordinator

Locations

1 EU/EEA country · 72 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 17 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