Chemotherapy For Metastatic Grade 3 Poorly Differentiated NEuroendocrine Carcinoma Of GastroEnteroPancreatic And Unknown Primary

NCT04325425 | Recruiting Phase 2 DMC

• 1 other identifier: PRODIGE 69
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 6

Brief Summary

there is a need for improving chemotherapy regimen for metastatic G3 NEC of GEP and Unknown origin and this goal may be achieved through more "personalized" chemotherapy regimen.the hypothesis is that mFOLFIRINOX regimen could be a good candidate for challenging the platinum-etoposide regimen in patients with metastatic G3 NEC of GEP or unknown origin. Furthermore, in order to get insights in the putative predictive biomarkers of efficacy of these two regimens, an effort toward a precise molecular characterization of these tumors is required in order to be able to define which subgroup of G3 NEC needs to be treated by which chemotherapy regimen. The FOLFIRINEC trial is set up in order to try to answer these questions

Conditions

Neuroendocrine Carcinoma

Outcome Measures

Primary Outcomes (1)

• median of progression free survival

  The primary endpoint is the median of progression-free survival. PFS is defined as the time interval between date of randomization and date of the first radiological progression (according to RECIST 1.1) or death due to any cause, whichever occurs first, according to investigator. Patient alive without progression will be censored at date of last follow-up visit.

  7.5 MONTHS

Secondary Outcomes (4)

• Progression-free survival (PFS)

  9 MONTHS

• Overall survival

  15 MONTHS

• Best objective response rate

  8 weeks after randomization

• Safety and tolerability profile: percentage of patients who experienced toxicities

  24 months after randomization of the last subject

Study Arms (2)

mFOLFIRINOX

EXPERIMENTAL

mFOLFIRINOX will be administered once every 14 days for up to 12 cycles. One cycle consists of 14 days (2 weeks) with injection on D1 of each cycle (D1=D15). Patients are eligible for repeated treatment cycles in the absence of disease progression and undue adverse events.

Drug: FOLFOXIRI Protocol

platinum - etoposide

ACTIVE COMPARATOR

Platinum-Etoposide regimen will be administered once every 21 days. Treatment will be continued for 6 to 8 cycles or 24 weeks maximum. One cycle consists of 21 days (3 weeks) with injection on D1 of each cycle (D1=D22). Patients are eligible for repeated treatment cycles in the absence of disease progression and undue adverse events.

Drug: Cisplatin injection

Interventions

FOLFOXIRI Protocol DRUG

Platinum-Etoposide regimen will be administered once every 21 days. Treatment will be continued for 6 to 8 cycles or 24 weeks maximum. One cycle consists of 21 days (3 weeks) with injection on D1 of each cycle (D1=D22). Patients are eligible for repeated treatment cycles in the absence of disease progression and undue adverse events.

Also known as: modified FOLFIRINOX

mFOLFIRINOX

Cisplatin injection DRUG

Cisplatin 100 mg/m2, IV infusion over 3 hours or Carboplatin AUC 5, IV infusion over 30 minutes on day 1 \[the dose of carboplatin will be determined for each cycle using the Calvert's formula (carboplatin dose (mg) = target AUC 5 x estimated glomerular filtration rate (eGFR, mL/min) + 25)\]; • Etoposide 100 mg/m² IV infusion over 1 hour on day 1,2 and 3

Also known as: Platinum - Etoposide, carboplatin injection

platinum - etoposide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Grade 3 neuroendocrine carcinoma or high grade MiNEN with a grade 3 poorly differentiated neuroendocrine carcinoma component ≥30% of gastro-entero-pancreatic or unknown primary
• Poorly differentiated
• Small cell or large cell or non-small cell or non- typeable
• Metastatic disease
• First-line, no prior therapy for metastatic disease, no prior use of carboplatin, oxaliplatin, cisplatin, etoposide, irinotecan and 5-fluorouracile
• At least one measurable lesion as assessed by CT-scan or MRI according to RECIST 1.1 guidelines
• Available tumor block
• ANC ≥ 1.5x109/l, platelet ≥ 100x109/l and hemoglobin \> 8 g/dl
• Total bilirubin ≤ 1.5N, AST ≤ 2.5N, ALT≤ 2.5N or AST/ALT ≤ 5N in case of liver metastases.
• Age ≥ 18 years
• ECOG Performance Status ≤ 1
• Signed and dated informed consent, and willing and able to comply with protocol requirements.
• 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
• Patient who is a beneficiary of the Social security system

You may not qualify if:

• Grade 3 well differentiated neuroendocrine tumor according to WHO 2017 classification
• Severe renal impairment (creatinine clearance less than 30 mL/min, MDRD)
• Partial or complete Dihydropyrimidine Dehydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)
• Gilbert's syndrome
• Pre-existing permanent neuropathy (NCI CTC V4.0 grade ≥2)
• Previously treated by chemotherapy or targeted therapy
• Combination with sorivudine and others analogues as brivudine (irreversibly inhibits the enzyme dihydropyrimidine dehydrogenase)
• Treatment with St John's Wort (Hypericum perforatum)
• Pregnant women or breastfeeding mother
• Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C
• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.
• 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
• vaccinations (live vaccine) within 30 days prior to start of study drugs
• Patient under guardianship and/or deprived of his/her freedom
• QT/QTc interval \> 450 msec for male and \> 470 msec for female at EKC.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead
• National Cancer Institute, France: collaborator

Study Sites (6)

Chu de Caen

Caen, 14033, France

RECRUITING

Chu Dijon Bourgogne

Dijon, 21000, France

RECRUITING

Institut de Cancérologie de Bourgogne

Dijon, 21000, France

RECRUITING

Chu de Limoges - Dupuytren

Limoges, 87042, France

RECRUITING

Centre Hospitalier de Saint Malo

St-Malo, 35403, France

RECRUITING

CH de Troyes

Troyes, 10003, France

RECRUITING

MeSH Terms

Conditions

Carcinoma, Neuroendocrine

Interventions

FOLFOXIRI protocol; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: mFOLFIRINOX (experimental arm) vs Platinum - Etoposide (standard arm)

Study Record Dates

• First Submitted: February 25, 2020
• First Posted: March 27, 2020
• Study Start: September 1, 2020
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: September 30, 2025

Record last verified: 2025-09

Locations

FR (6)