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
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
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
Parallel
FOLFOXIRI Protocol
DrugPlatinum-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.
Cisplatin injection
DrugCisplatin 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
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.
Progression-free survival (PFS)
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 the centralized review.
Overall survival
OS is defined as the time interval between date of randomization and date of death (whatever the cause). Patients alive will be censored at date of last news.
Best objective response rate
The best objective response rate is defined as the proportion of patients with an objective response (Complete response (CR) + Partial response (PR)) at any evaluation during the treatment, according to RECIST 1.1.
Safety and tolerability profile: percentage of patients who experienced toxicities
Safety profile is defined as the percentage of patients who experienced toxicities and grading of these toxicities. Toxicities will be presented as the number of patients presenting at least an episode of toxicity by maximum grade. Toxicity grading will follow NCI-CTC V4 guidelines
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Centre Hospitalier Universitaire Dijon
Lead sponsor
National Cancer Institute, France
Collaborator
