METASTATIC GRADE 3 POORLY DIFFERENTIATED NEUROENDOCRINE CARCINOMA OF GASTRO ENTERO PANCREATIC AND UNKNOWN PRIMARY
Conditions
Interventions
Trade Name: FLUOROURACILE TEVA
Product Name: FLUOROURACILE TEVA
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: FLUOROURACIL SODIUM
Current Sponsor code: fluorouracil
Concentration uni
Sponsors
CHU DIJON
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •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 haemoglobin > 8 g/dl •Total bilirubin = 1.5N, AST = 2.5N, ALT= 2.5N or AST/ALT = 5N in case of liver metastass. •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 6 months following administration of the last dose of the study medicinal product •Patient who is a beneficiary of the Social security system Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 214 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: •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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.;Secondary Objective: PFS according to the centralized review (RECIST v1.1 criteria) Best objective response rate (ORR) Median overall survival (OS) Safety according to NCI CTC V4.0 Dose-reductions Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L 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. Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…);Primary end point(s): To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.;Timepoint(s) of evaluation of this end point: 8 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •PFS according to the centralized review (RECIST v1.1 criteria) •Best objective response rate (ORR) •Median overall survival (OS) •Safety according to NCI CTC V4.0 •Dose-reductions •Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L •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. •Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype •Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…);Timepoint(s) of evaluation of this end point: 8 months | — |
Countries
France
Contacts
Public ContactLila GABA
fédération francophone de cancérologie digestive
Outcome results
None listed