Clinical trial • Phase II • Oncology

OXALIPLATIN for Metastatic grade 3 poorly differentiated gastroenteropancreatic neuroendocrine carcinoma | Neuroendocrine carcinoma of unknown primary

Phase II trial of OXALIPLATIN for Metastatic grade 3 poorly differentiated gastroenteropancreatic neuroendocrine carcinoma | Neuroendocrine carcinoma of u…

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Metastatic grade 3 poorly differentiated gastroenteropancreatic neuroendocrine carcinoma | Neuroendocrine carcinoma of unknown primary
Trial Stage
Phase II
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
26-09-2024
First CTIS Authorization Date
18-10-2024

Trial design

Randomised, mfolfirinox versus platinum-etoposide. mfolfirinox components in record: oxaliplatin (max dose 85 mg/m2), irinotecan (max dose 150 mg/m2), fluorouracil (max daily amount 1200 mg/m2). platinum-etoposide components in record: cisplatin (max dose 100 mg/m2), etoposide (max daily dose 100 mg/m2; max total dose 300 mg/m2). schedule not specified in the ctis record.-controlled Phase II trial in France.

Randomised
Yes
Comparator
mFOLFIRINOX versus platinum-etoposide. mFOLFIRINOX components in record: oxaliplatin (max dose 85 mg/m2), irinotecan (max dose 150 mg/m2), fluorouracil (max daily amount 1200 mg/m2). Platinum-etoposide components in record: cisplatin (max dose 100 mg/m2), etoposide (max daily dose 100 mg/m2; max total dose 300 mg/m2). Schedule not specified in the CTIS record.
Target Sample Size
218

Eligibility

Recruits 218 Vulnerable populations are not selected. Patients under guardianship and/or deprived of his/her freedom are explicitly excluded. Participants must be adults (Age ≥ 18 years) and must provide signed and dated informed consent; no paediatric consent/assent procedures are applicable..

Pregnancy Exclusion
Pregnant women or breastfeeding mother
Vulnerable Population
Vulnerable populations are not selected. Patients under guardianship and/or deprived of his/her freedom are explicitly excluded. Participants must be adults (Age ≥ 18 years) and must provide signed and dated informed consent; no paediatric consent/assent procedures are applicable.

Inclusion criteria

  • {"criterion_text":"- Grade 3 neuroendocrine carcinoma (Ki67>20%) or high grade MiNEN with a grade 3 poorly differentiated neuroendocrine carcinoma\n- Total bilirubin ≤ 1.5N, AST ≤ 2.5N, ALT≤ 2.5N or AST and ALT ≤ 5N in case of liver metastasis.\n- Age ≥ 18 years\n- Signed and dated informed consent, and willing and able to comply with protocol requirements.\n- 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\n- Patient who is a beneficiary of the Social security system\n- Primary gastro-entero-pancreatic or unknown primary\n- Small cell or large cell or non-small cell or non- typeable neuroendocrine carcinoma\n- Metastatic disease\n- ECOG performance status ≤ 1\n- First line treatment for metastatic disease. No prior chemotherapy or systemic therapy for management of metastatic disease or primary tumor\n- At least one measurable lesion as assessed by CT-scan or MRI according to RECIST 1.1 guidelines\n- Available tumor block\n- ANC ≥ 1.5x109/l, platelet ≥ 100x109/l and haemoglobin > 8 g/dl"}

Exclusion criteria

  • {"criterion_text":"- Grade 3 well differentiated neuroendocrine tumor according to WHO 2017 classification\n- Treatment with St John's Wort (Hypericum perforatum)\n- Pregnant women or breastfeeding mother\n- Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C\n- History of prior malignancy in the three yars before randomization, except for cured non-melanoma skin cancer and cured in situ cervical carcinoma.\n- 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\n- vaccinations (live vaccine) within 30 days prior to start of study drugs\n- Patient under guardianship and/or deprived of his/her freedom\n- QTc interval > 450 msec for male and > 470 msec for female at EKC.\n- K+ < LLN, Mg²+ < LLN, Ca²+ < LLN\n- History or know hypersensitivity to any of the study chemotherapy agents, or their excipients.\n- Severe renal impairment (creatinine clearance less than 30 mL/min, Cockroft and Gault)\n- Patient already participating in another clinical trial who is currently being treated or whose treatment was completed less than four weeks prior to inclusion.\n- ECOG performance status > 1\n- Partial or complete Dihydropyrimidine Dehydrogenase (DPD) deficiency (uracilemia ≥ 16 ng/mL)\n- Known Gilbert's syndrome\n- Pre-existing permanent neuropathy (NCI CTC V4.0 grade ≥2)\n- Previously treated by chemotherapy or targeted therapy\n- Symptomatic brain metastases patient with asymptomatic brain metastases or under stable corticosteroid doses for at least 2 weeks before randomization can be included.\n- Combination with sorivudine and others analogues of dihydropyrimidine dehydrogenase)"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- To compare the progression-free survival (PFS) with mFOLFIRINOX regimen versus platinum - etoposide regimen according to the investigator using RECIST v1.1 criteria.","definition_or_measurement_approach":"Progression-free survival (PFS) assessed by the investigator using RECIST v1.1 criteria."}

Secondary endpoints

  • {"endpoint_text":"- PFS according to the centralized review (RECIST v1.1 criteria)","definition_or_measurement_approach":"Progression-free survival assessed by centralized radiological review using RECIST v1.1."}
  • {"endpoint_text":"- Best objective response rate (ORR)","definition_or_measurement_approach":"Objective response rate measured by RECIST v1.1."}
  • {"endpoint_text":"- Median overall survival (OS)","definition_or_measurement_approach":"Overall survival measured as time from randomization to death from any cause."}
  • {"endpoint_text":"- Safety according to NCI CTC V4.0","definition_or_measurement_approach":"Adverse events graded per NCI CTCAE v4.0."}
  • {"endpoint_text":"- Dose-reductions","definition_or_measurement_approach":"Number and incidence of dose reductions during treatment."}
  • {"endpoint_text":"- Quality of life assessed by EORTC QLQ-C30 and EQ-5D-5L","definition_or_measurement_approach":"Patient-reported quality of life instruments: EORTC QLQ-C30 and EQ-5D-5L according to their scoring manuals."}
  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Generation of molecular profiling report within 2 months of tumor sample submission; molecular tumor board report provided to treating physician."}
  • {"endpoint_text":"- Frequency of Rb loss in G3 NEC irrespective of the SC or LC subtype","definition_or_measurement_approach":"Assessment of Rb expression loss frequency by immunohistochemistry/genomic assessment across enrolled samples."}
  • {"endpoint_text":"- Correlation of ORR, PFS and OS under both chemotherapy regimens with molecular alterations (Rb, TP53, MSH2…)","definition_or_measurement_approach":"Correlation analyses between clinical outcomes (ORR, PFS, OS) and detected molecular alterations (including Rb, TP53, MSH2, etc.)."}

Recruitment

Planned Sample Size
218
Recruitment Window Months
101
Consent Approach
Adults (≥18 years) must provide signed and dated informed consent prior to participation. Subject information and informed consent form documents are included in the submission (L1_SIS and ICF and translated copy L1_SIS and ICF_tc); questionnaires (EORTC QLQ-C30, EQ-5D-5L) are provided as patient-facing documents. No paediatric assent process is applicable.

Geography

Total Number Of Sites
73
Total Number Of Participants
218

France

Earliest CTIS Part Ii Submission Date
21-08-2024
Latest Decision Or Authorization Date
23-09-2025
Processing Time Days
398
Number Of Sites
73
Number Of Participants
218

Sites

Site Name
Institut De Cancerologie De Lorraine
Department Name
oncology
Contact Person Name
Aurélien LAMBERT
Contact Person Email
a.lambert@nancy.unicancer.fr
Site Name
Centre Hospitalier De La Cote Basque
Department Name
gastro oncology
Contact Person Name
Franck AUDEMAR
Contact Person Email
faudemar@ch-cotebasque.fr
Site Name
CHU Rennes Pontchaillou Hospital
Department Name
gastro enterology
Contact Person Name
Astrid LIEVRE
Contact Person Email
astrid.lievre@chu-rennes.fr
Site Name
Institut Mutualiste Montsouris
Department Name
oncology
Contact Person Name
Christophe LOUVET
Contact Person Email
christophe.louvet@imm.fr
Site Name
Centre Hospitalier D Avignon
Department Name
oncology
Contact Person Name
Thibault BROTELLE
Site Name
Chi Les Hopitaux Du Leman
Department Name
oncology
Contact Person Name
POMMERET Fanny
Site Name
Centre Hospitalier Universitaire Rouen
Department Name
gastro enterology
Contact Person Name
Frédéric DI FIORE
Contact Person Email
Frederic.Di-Fiore@chu-rouen.fr
Site Name
CHU d'Estaing
Department Name
oncology
Contact Person Name
Denis PEZET
Contact Person Email
dpezet@chu-clermontferrand.fr
Site Name
CH St Malo - Hôpital Broussais
Department Name
Hepato-gastroenterology
Contact Person Name
Romain DESGRIPPES
Contact Person Email
r.desgrippes@ch-st-malo.fr
Site Name
Courlancy Sante
Department Name
oncology
Contact Person Name
Nicolas JOVENIN
Contact Person Email
njovenin@iccreims.fr
Site Name
Hospital Hotel Dieu
Department Name
gastro enterology
Contact Person Name
Tamara MATYSIAK-BUDNIK
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Gastroenterology
Contact Person Name
Hédia BRIXI
Contact Person Email
hbrixi@chu-reims.fr
Site Name
Hôpital Privé Paul D' Egine
Department Name
oncology
Contact Person Name
Faouzia SAADANA
Contact Person Email
faouzia.saadana@gmail.com
Site Name
Centre Regional Lutte Contre Le Cancer
Department Name
Gastroenterology
Contact Person Name
Meher BEN ABDELGHANI
Contact Person Email
m.ben-abdelghani@icans.eu
Site Name
Centre Hospitalier De Pau
Department Name
Hepato-gastroenterology and oncology
Contact Person Name
Juliette THAURY
Contact Person Email
juliette.thaury@ch-pau.fr
Site Name
Hopital Saint Antoine
Department Name
gastro enterology
Contact Person Name
Pauline AFCHAIN
Contact Person Email
pauline.afchain@aphp.fr
Site Name
Centre Hospitalier De Perpignan
Department Name
Gastroenterology
Contact Person Name
Faiza KHEMISSA AKOUZ
Contact Person Email
faiza.khemissa@ch-perpignan.fr
Site Name
Hopital Europeen Marseille
Department Name
gastro entero oncology
Contact Person Name
Yves RINALDI
Contact Person Email
y.rinaldi@hopital-europeen.fr
Site Name
Hopital Huriez
Department Name
Gastroenterology
Contact Person Name
Stéphane CATTAN
Contact Person Email
stephane.cattan@chu-lille.fr
Site Name
Hopital Prive Sainte Marie Chalon
Department Name
Médical Oncology
Contact Person Name
Adrien MELIS
Contact Person Email
melisadrien@gmail.com
Site Name
Centre Hospitalier D Auxerre
Department Name
oncology
Contact Person Name
Anne-Laure VILLING
Contact Person Email
alvilling@ch-auxerre.fr
Site Name
Institut Paoli Calmettes
Department Name
oncology
Contact Person Name
Patricia NICCOLI
Contact Person Email
patricia.niccoli@ap-hm.fr
Site Name
Centre Hospitalier D Albi
Department Name
oncology
Contact Person Name
Corinne COUTEAU
Contact Person Email
corinne.couteau@ch-albi.fr
Site Name
Centre Leon Berard
Department Name
oncology
Contact Person Name
Christelle DE LAFOUCHARDIERE
Site Name
C.H.U. de Montpellier - Hopital Saint Eloi
Department Name
hépato gastro enterology
Contact Person Name
Eric ASSENAT
Contact Person Email
e-assenat@chu-montpellier.fr
Site Name
Sainte Catherine Institut Du Cancer Avignon-Provence
Department Name
oncology
Contact Person Name
Laurent MINEUR
Contact Person Email
l.mineur@isc84.org
Site Name
CHU Amiens - Groupe Hospitalier Sud
Department Name
Gastroenterology
Contact Person Name
Vincent HAUTEFEUILLE
Site Name
Institut Gustave Roussy
Department Name
Service d'Oncologie Endocrinienne
Contact Person Name
Julien HADOUX
Contact Person Email
julien.hadoux@gustaveroussy.fr
Site Name
Polyclinique de l'Ormeau
Department Name
oncology
Contact Person Name
Philippe AYELA
Contact Person Email
philippe.ayela@sfr.fr
Site Name
Médipôle Hôpital Mutualiste Lyon-Villeurbanne
Department Name
gastro enterology
Contact Person Name
Marie-Anne GUILLAUMOT
Contact Person Email
ma.guillaumot@gelmad.fr
Site Name
Centre Hospitalier Bretagne Atlantique
Department Name
gastro enterology
Contact Person Name
Laure RABILLOUD
Site Name
Hospital Edouard Herriot
Department Name
gastro entero oncology
Contact Person Name
Thomas WALTER
Contact Person Email
thomas.walter@chu-lyon.fr
Site Name
Centre Hospitalier Metropole Savoie
Department Name
oncology
Contact Person Name
Olivier BERTHELET
Site Name
Centre Antoine Lacassagne
Department Name
Médical Oncology
Contact Person Name
Claire JARAUDIAS
Site Name
Union Mut Gestion Groupe Hosp Mutualiste De Grenoble
Department Name
Médical Oncology
Contact Person Name
Hélène FLESCH
Contact Person Email
helene.flesch@avec.fr
Site Name
Centre Hospitalier de la Région d'Annecy
Department Name
hépato gastro enterology
Contact Person Name
Mathieu BACONNIER
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
Gastroenterology
Contact Person Name
Thierry LECOMTE
Contact Person Email
thierry.lecomte@univ-tours.fr
Site Name
Centre Hospitalier Universitaire De Toulouse
Department Name
Digestive Oncology
Contact Person Name
Rosine GUIMBAUD
Contact Person Email
guimbaud.r@chu-toulouse.fr
Site Name
Centre Hospitalier De Boulogne Sur Mer
Department Name
Digestive Oncology
Contact Person Name
Vincent BOURGEOIS
Contact Person Email
v.bourgeois@ch-boulogne.fr
Site Name
Centre Hospitalier Universitaire D Orleans
Department Name
Medical Oncology
Contact Person Name
Heba DAWOOD
Contact Person Email
heba.dawood@chr-orleans.fr
Site Name
Centre Hospitalier Jean Rougier
Department Name
oncology rhumatology
Contact Person Name
Slim LASSOUED
Contact Person Email
slim.lassoued@ght-lot.fr
Site Name
Hôpital Franco-Britannique-Fondation Cognacq-Jay
Department Name
oncology
Contact Person Name
Benoist CHIBAUDEL
Contact Person Email
benoist.chibaudel@ihfb.org
Site Name
Centre Hospitalier Sud Francilien
Department Name
oncology
Contact Person Name
Samy LOUAFI
Contact Person Email
samy.louafi@chsf.fr
Site Name
INSTITUT DE CANCEROLOGIE DE BOURGOGNE GRRECC
Department Name
oncology
Contact Person Name
Véronique LORGIS
Contact Person Email
vlorgis@icb-cancer.fr
Site Name
Hopital Prive Des Cotes D'armor
Department Name
oncology
Contact Person Name
Jérôme MARTIN-BABAU
Contact Person Email
j.martin@cario-sante.fr
Site Name
Institut Godinot
Department Name
Medical Oncology
Contact Person Name
Damien BOTSEN
Site Name
Hopital Prive D Antony
Department Name
Hepato-Gastro-Entérology
Contact Person Name
Anne THIROT-BIDAULT
Contact Person Email
a.t.bidault@gmail.com
Site Name
Hôpital NOVO - Site de Pontoise
Department Name
oncology
Contact Person Name
Waad AL SHEIKH
Contact Person Email
waad.alsheikh@ght-novo.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Hepato-gastroentero oncology
Contact Person Name
Côme LEPAGE
Contact Person Email
come.lepage@u-bourgogne.fr
Site Name
Hopital Jean Minjoz
Department Name
Médical Oncology
Contact Person Name
Fabien CALCAGNO
Contact Person Email
calcagno@gmail.com
Site Name
Centre Hospitalier Universitaire D'Angers
Department Name
Gastroenterology
Contact Person Name
Guillaume ROQUIN
Contact Person Email
Guillaume.Roquin@chu-angers.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Digestive Oncology
Contact Person Name
Hélène SENELLART
Site Name
Centre Hospitalier Departemental Vendee
Department Name
Gastroenterology
Contact Person Name
Paul GIROT
Contact Person Email
paul.girot@chd-vendee.fr
Site Name
CHU De Martinique
Department Name
endocrinology and oncology
Contact Person Name
Audrey ZABULON
Site Name
Centre Hospitalier De Troyes
Department Name
oncology
Contact Person Name
Jesus MONTESINOS MUNOZ
Contact Person Email
jesus.montesinos@hcs-sante.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
oncology
Contact Person Name
Denis SMITH
Contact Person Email
denis.smith@chu-bordeaux.fr
Site Name
Centre Hospitalier Universitaire De Saint Etienne
Department Name
hépato gastro enterology/digestive oncology
Contact Person Name
Jean-Marc PHELIP
Site Name
Centre Hospitalier Intercommunal De Mont De Marsan Et Du Pays Des Sources
Department Name
hépato gastro enterology
Contact Person Name
Morgan ANDRE
Contact Person Email
morgan.andre@ch-mdm.fr
Site Name
Hoptial La Timone
Department Name
Digestive Oncology
Contact Person Name
Laétitia DAHAN
Site Name
CHR d'Orleans
Department Name
Hepato-gastroenterology and digestive oncology
Contact Person Name
Barbara DAUVOIS
Contact Person Email
barbara.dauvois@chr-orleans.fr
Site Name
Hôpital de Mercy
Department Name
Hepato-gastroenterology
Contact Person Name
Laurence DELIQUE
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Gastroenterology
Contact Person Name
Karine BOUHIER LEPORRIER
Contact Person Email
bouhierleporrier-k@chu-caen.fr
Site Name
Centre Hospitalier Universitaire De Poitiers
Department Name
oncology
Contact Person Name
Aurélie FERRU
Contact Person Email
a.ferru@chu-poitiers.fr
Site Name
Hopital Beaujon
Department Name
gastro enterology
Contact Person Name
Louis DE MESTIER
Contact Person Email
louis.demestier@aphp.fr
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
gastro enterology
Contact Person Name
Christelle D'ENGREMONT
Contact Person Email
CDengremont@chu-grenoble.fr
Site Name
Groupe Hospitalier Bretagne Sud
Department Name
Hepato-gastroenterology
Contact Person Name
Florence LE ROY
Contact Person Email
f.leroy@ghbs.bzh
Site Name
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Department Name
oncology
Contact Person Name
nabil BABA-HAMED
Contact Person Email
nbaba-hamed@hpsj.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
oncology
Contact Person Name
Frédéric THUILLIER
Site Name
Hôpital Avicenne
Department Name
hépato gastro enterology/digestive oncology
Contact Person Name
Florence MARY
Contact Person Email
florence.mary@aphp.fr
Site Name
Centre Hospitalier De Colmar
Department Name
gastroenterology
Contact Person Name
Marion BOLLIET
Contact Person Email
marion.bolliet@ch-colmar.fr
Site Name
Centre Hospitalier de l'Agglomération de Nevers
Department Name
oncology
Contact Person Name
Yacine HADJARAB
Contact Person Email
yacine.hadjarab@wanadoo.fr
Site Name
Assistance Publique Hopitaux de Paris – Hopital Cochin
Department Name
Gastroenterology
Contact Person Name
Romain CORIAT
Contact Person Email
romain.coriat@aphp.fr

Sponsor

Primary sponsor

Full Name
Centre Hospitalier Universitaire De Dijon
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
OXALIPLATINE HOSPIRA 5 mg/ml, solution à diluer pour perfusion
Active Substance
OXALIPLATIN
Modality
Small molecule
Routes Of Administration
IV INFUSION
Route
IV INFUSION
Authorisation Status
Authorised
Maximum Dose
85 mg/m2
Investigational Product Name
Irinotecan Kabi 20 mg/ml concentrate for solution for infusion
Active Substance
IRINOTECAN HYDROCHLORIDE TRIHYDRATE
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Authorisation Status
Authorised
Maximum Dose
150 mg/m2
Investigational Product Name
ETOPOSIDE TEVA 200 mg/10 ml, solution injectable pour perfusion
Active Substance
ETOPOSIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
INTRAVENOUS INFUSION
Authorisation Status
Authorised
Maximum Dose
100 mg/m2 (max total dose reported 300 mg/m2)
Investigational Product Name
FLUOROURACILE TEVA 1000 mg/20 ml, solution à diluer pour perfusion
Active Substance
FLUOROURACIL
Modality
Small molecule
Routes Of Administration
INTRAVENIOUS INFUSION
Route
INTRAVENIOUS INFUSION
Authorisation Status
Authorised
Maximum Dose
1200 mg/m2 (max total dose reported 2400 mg/m2)
Investigational Product Name
Cisplatine Teva 1 mg/ml concentraat voor oplossing voor infusie.
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS PERFUSION USE
Route
INTRAVENOUS PERFUSION
Authorisation Status
Authorised
Maximum Dose
100 mg/m2
Combination Treatment
Yes

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