RecruitingPhase 2NCT04325425

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

Folfirinox Versus Platinum - Etoposide as First Line Chemotherapy for Metastatic Grade 3 Poorly Differentiated Neuroendocrine Carcinoma of Gastro Entero Pancreatic and Unknown Primary Associated With Molecular Profiling for Therapeutic Targets & Predictive Biomarkers Identification

Sponsor

Centre Hospitalier Universitaire Dijon

Enrollment

218 participants

Start Date

Sep 1, 2020

Study Type

INTERVENTIONAL

Conditions

Neuroendocrine Carcinoma

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

Eligibility

Min Age: 18 Years

Inclusion Criteria14

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

Exclusion Criteria18

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
Brain metastases unless they are asymptomatic or under stable corticosteroid doses for 2 weeks otherwise. Radiation therapy prior to inclusion is required if symptomatic.
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.
K+ \< LLN, Mg²+ \< LLN, Ca²+ \< LLN
History or know hypersensitivity to any of the study chemotherapy agents, or their excipients

Interventions

DRUGFOLFOXIRI Protocol

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.

DRUGCisplatin injection

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