Clinical trial • Phase III • Oncology|Gastroenterology

IRINOTECAN HYDROCHLORIDE for Locally advanced resectable rectal cancer

Phase III trial of IRINOTECAN HYDROCHLORIDE for Locally advanced resectable rectal cancer.

Overview

Trial Therapeutic Area
Oncology|Gastroenterology
Trial Disease
Locally advanced resectable rectal cancer
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
05-04-2024
First CTIS Authorization Date
21-05-2024

Trial design

Randomised, two arms: arm a: preoperative chemotherapy only. arm b: chemotherapy followed by chemoradiotherapy (pelvic irradiation). chemotherapy agents listed in trial documents include irinotecan, oxaliplatin, fluorouracil and calcium folinate; specific arm regimens/doses/schedules not detailed in provided record.-controlled Phase III trial across 46 sites in France.

Randomised
Yes
Comparator
Two arms: Arm A: preoperative chemotherapy only. Arm B: chemotherapy followed by chemoradiotherapy (pelvic irradiation). Chemotherapy agents listed in trial documents include irinotecan, oxaliplatin, fluorouracil and calcium folinate; specific arm regimens/doses/schedules not detailed in provided record.
Target Sample Size
540
Trial Duration For Participant
1095

Eligibility

Recruits 540 Protected adults are excluded (listed under exclusion criteria). Informed consent must be signed; participants must be 18 years or older. No paediatric/assent procedures described and isVulnerablePopulationSelected is false..

Pregnancy Exclusion
Pregnancy or breastfeeding
Vulnerable Population
Protected adults are excluded (listed under exclusion criteria). Informed consent must be signed; participants must be 18 years or older. No paediatric/assent procedures described and isVulnerablePopulationSelected is false.

Inclusion criteria

  • {"criterion_text":"- Histologically proven middle or low rectal carcinoma, ≤ 12 cm from the anal verge on MRI (sagittal slide)\n- cT3N0 and/or cT1-T3N+ on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound)\n- Pretreatment predictive circumferential margin > 2mm on pretreatment imaging work up (pelvic contrast enhanced MRI)\n- Patients must be 18 years old or older\n- A World Health Organization (WHO/ECOG) performance status of 0 or 1\n- Informed consent signed\n- Patients of childbearing / reproductive potential should use adequate birth control measures during the study treatment period and for at least 6 months after the last study treatment"}

Exclusion criteria

  • {"criterion_text":"- Rectal tumor > 12 cm from the anal verge on MRI (sagittal slide)\n- Contraindication to irinotecan : inflammatory bowel disease, bilirubin serum level > 3 times the upper limit of the normal rate, severe bone marrow insufficiency, WHO/ECOG performence status > 2\n- Concomitant treatment with millepertuis\n- Contraindication to oxaliplatin : bone marrow insufficiency before treatment initiation (neutrophil count <2x109/L and/or platelet count <100x109/L), peripheral neuropathy with permanent invalidity before treatment initiation\n- Contraindications to folinic acid : Biermer anemia and other anemia related to B12 vitamin insufficiency\n- Contraindications to capecitabine : severe renal insufficiency (Creatinin clearance <30 ml/min), complete and permanent insufficiency in dihydropyrimidine dehydrogenase\n- Live attenuated vaccine should not be used during and 6 months after preoperative treatment\n- Previous colorectal cancer\n- Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years\n- Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial\n- Protected adults\n- cT4 tumor on pretreatment imaging work up (pelvic contrast enhanced MRI and/or endorectal ultrasound) or involvement of external sphincter\n- Pregnancy or breastfeeding\n- Patient with no national health or universal plan affiliation coverage\n- Circumferential margin ≤ 2 mm on pretreatment imaging work up (pelvic contrast enhanced MRI)\n- Metastatic disease\n- Prior pelvic irradiation or any contraindication to pelvic irradiation\n- Contraindication to oxaliplatin or irinotecan or 5FU based chemotherapy\n- Concomitant treatment with warfarin is contraindicated and warafarin must be replaced whenever possible to allow for inclusion\n- Recent or concomitant treatment with brivudine is contraindicated\n- Contraindications to 5-FU: complete and permanent insufficiency in dihydropyrimidine dehydrogenase, bone marrow insufficiency, chronic and severe infection"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- The main endpoint of this phase III study is 3-year progression-free survival from the time to randomization.","definition_or_measurement_approach":"3-year progression-free survival measured from time of randomization (PFS at 3 years)."}

Recruitment

Planned Sample Size
540
Recruitment Window Months
138
Consent Approach
Informed consent must be signed by participant; participants must be 18 years or older. A subject information sheet and informed consent form for adults is provided (document L1_SIS and ICF adults). No assent/minor consent described; languages not specified.

Geography

Total Number Of Sites
46
Total Number Of Participants
540

France

Earliest CTIS Part Ii Submission Date
12-03-2024
Latest Decision Or Authorization Date
17-04-2026
Processing Time Days
766
Number Of Sites
46
Number Of Participants
540

Sites

Site Name
Besancon University Hospital Center
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Zaher LAKKIS
Principal Investigator Email
zlakkis@chu-besancon.fr
Contact Person Name
Zaher LAKKIS
Contact Person Email
zlakkis@chu-besancon.fr
Site Name
Groupement De Cooperation Sanitaire Risssa Recherche & Innovation Sante Sarcelles
Department Name
Radiotherapy
Principal Investigator Name
Anne LARROUY
Principal Investigator Email
a.larrouy@icpn.care
Contact Person Name
Anne LARROUY
Contact Person Email
a.larrouy@icpn.care
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Colorectal surgery
Principal Investigator Name
Massimo GIACCA
Principal Investigator Email
massimo.giacca@aphp.fr
Contact Person Name
Massimo GIACCA
Contact Person Email
massimo.giacca@aphp.fr
Site Name
IHFB Cognacq Jay
Department Name
Medical Oncology
Principal Investigator Name
Benoist Chibaudel CHIBAUDEL
Principal Investigator Email
benoist.chibaudel@ihfb.org
Contact Person Name
Benoist Chibaudel CHIBAUDEL
Contact Person Email
benoist.chibaudel@ihfb.org
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Digestive surgery
Principal Investigator Name
Uho MARCHESE
Principal Investigator Email
ugo.marchese@aphp.fr
Contact Person Name
Uho MARCHESE
Contact Person Email
ugo.marchese@aphp.fr
Site Name
Centre Hospitalier Universitaire De Rennes
Department Name
Digestive surgery
Principal Investigator Name
Géraldine PERKINS
Principal Investigator Email
geraldine.perkins@chu-rennes.fr
Contact Person Name
Géraldine PERKINS
Site Name
Centre Hospitalier Simone Veil De Beauvais
Department Name
Digestive surgery
Principal Investigator Name
Francois MAUVAIS
Principal Investigator Email
rechercheclinique@ch-beauvais.fr
Contact Person Name
Francois MAUVAIS
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Radiation Oncology
Principal Investigator Name
Florence HUGUET
Principal Investigator Email
florence.huguet@aphp.fr
Contact Person Name
Florence HUGUET
Contact Person Email
florence.huguet@aphp.fr
Site Name
Institut Gustave Roussy
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Leonor BENHAIM
Principal Investigator Email
leonor.benhaim@gustaveroussy.fr
Contact Person Name
Leonor BENHAIM
Site Name
Sainte Catherine Institut Du Cancer Avignon-Provence
Department Name
Radiation Oncology
Principal Investigator Name
Laurent MINEUR
Principal Investigator Email
l.mineur@isc84.org
Contact Person Name
Laurent MINEUR
Contact Person Email
l.mineur@isc84.org
Site Name
University Hospital Of Clermont-Ferrand
Department Name
Digestive surgery
Principal Investigator Name
Karine POIROT
Principal Investigator Email
kpoirot@chu-clermontferrand.fr
Contact Person Name
Karine POIROT
Contact Person Email
kpoirot@chu-clermontferrand.fr
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Sylvain MANFREDI
Principal Investigator Email
sylvain.manfredi@chu-dijon.fr
Contact Person Name
Sylvain MANFREDI
Contact Person Email
sylvain.manfredi@chu-dijon.fr
Site Name
Centre Hospitalier Universitaire Amiens Picardie
Department Name
Digestive surgery
Principal Investigator Name
Jean-Marc REGIMBEAU
Principal Investigator Email
regimbeau.jean-marc@chu-amiens.fr
Contact Person Name
Jean-Marc REGIMBEAU
Site Name
Hopital Prive Jean Mermoz
Department Name
Digestive oncology
Principal Investigator Name
Pascal ARTRU
Principal Investigator Email
dr.artru@wanadoo.fr
Contact Person Name
Pascal ARTRU
Contact Person Email
dr.artru@wanadoo.fr
Site Name
Clinique Tivoli Ducos
Department Name
Digestive and parietal surgery
Principal Investigator Name
Quentin DENOST
Principal Investigator Email
q.denost@bordeaux-colorectal-institute.fr
Contact Person Name
Quentin DENOST
Site Name
Centre Hospitalier Universitaire Grenoble Alpes
Department Name
Digestive surgery
Principal Investigator Name
Jean-Luc FAUCHERON
Principal Investigator Email
jlfaucheron@chu-grenoble.fr
Contact Person Name
Jean-Luc FAUCHERON
Contact Person Email
jlfaucheron@chu-grenoble.fr
Site Name
CHRU De Nancy
Department Name
Digestive surgery
Principal Investigator Name
Adeline GERMAIN
Principal Investigator Email
a.germain@chru-nancy.fr
Contact Person Name
Adeline GERMAIN
Contact Person Email
a.germain@chru-nancy.fr
Site Name
Institut Regional Du Cancer De Montpellier
Department Name
Surgical Oncology
Principal Investigator Name
Philippe ROUANET
Principal Investigator Email
philippe.rouanet@icm.unicancer.fr
Contact Person Name
Philippe ROUANET
Site Name
Centre Antoine Lacassagne
Department Name
Digestive oncology
Principal Investigator Name
Eric FRANCOIS
Principal Investigator Email
eric.francois@nice.unicancer.fr
Contact Person Name
Eric FRANCOIS
Site Name
Centre Hospitalier Regional De Marseille
Department Name
General and digestive surgery
Principal Investigator Name
Laura BEYER-BERJOT
Principal Investigator Email
laura.beyer@ap-hm.fr
Contact Person Name
Laura BEYER-BERJOT
Contact Person Email
laura.beyer@ap-hm.fr
Site Name
Centre Hospitalier Universitaire De Bordeaux
Department Name
Colorectal surgery
Principal Investigator Name
Benjamin FERNANDEZ
Principal Investigator Email
benjamin.fernandez@chu-bordeaux.fr
Contact Person Name
Benjamin FERNANDEZ
Site Name
Assistance Publique Hopitaux De Paris
Department Name
General and digestive surgery
Principal Investigator Name
Jérémie LEFEVRE
Principal Investigator Email
jeremie.lefevre@aphp.fr
Contact Person Name
Jérémie LEFEVRE
Contact Person Email
jeremie.lefevre@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Frédérique PESCHAUD
Principal Investigator Email
frederique.peschaud@aphp.fr
Contact Person Name
Frédérique PESCHAUD
Contact Person Email
frederique.peschaud@aphp.fr
Site Name
Institut De Cancerologie De L Ouest
Department Name
Surgical Oncology
Principal Investigator Name
Frédéric DUMONT
Principal Investigator Email
frederic.dumont@ico.unicancer.fr
Contact Person Name
Frédéric DUMONT
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Surgical Oncology
Principal Investigator Name
Frédéric DUMONT
Principal Investigator Email
frederic.dumont@ico.unicancer.fr
Contact Person Name
Frédéric DUMONT
Site Name
Centre Hospitalier Universitaire De Dijon
Department Name
Digestive oncology
Principal Investigator Name
Sylvain MANFREDI
Principal Investigator Email
sylvain.manfredi@chu-dijon.fr
Contact Person Name
Sylvain MANFREDI
Contact Person Email
sylvain.manfredi@chu-dijon.fr
Site Name
Les Hopitaux Universitaires De Strasbourg
Department Name
Digestive surgery
Principal Investigator Name
Benoît ROMAIN
Principal Investigator Email
benoit.romain@chru-strasbourg.fr
Contact Person Name
Benoît ROMAIN
Site Name
Institut De Cancerologie De Lorraine
Department Name
Surgery
Principal Investigator Name
Cécilia CERIBELLI
Principal Investigator Email
c.ceribelli@nancy.unicancer.fr
Contact Person Name
Cécilia CERIBELLI
Contact Person Email
c.ceribelli@nancy.unicancer.fr
Site Name
Institut Mutualiste Montsouris
Department Name
Digestive surgery
Principal Investigator Name
Christine DENET
Principal Investigator Email
christine.denet@imm.fr
Contact Person Name
Christine DENET
Contact Person Email
christine.denet@imm.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Digestive surgery
Principal Investigator Name
Hadrien TRANCHART
Principal Investigator Email
hadrien.tranchart@aphp.fr
Contact Person Name
Hadrien TRANCHART
Contact Person Email
hadrien.tranchart@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Stéphane BENOIST
Principal Investigator Email
stephane.benoist@aphp.fr
Contact Person Name
Stéphane BENOIST
Contact Person Email
stephane.benoist@aphp.fr
Site Name
Centre Hospitalier Regional Universitaire De Tours
Department Name
General and digestive surgery
Principal Investigator Name
Mehdi OUAISSI
Principal Investigator Email
m.ouaissi@chu-tours.fr
Contact Person Name
Mehdi OUAISSI
Contact Person Email
m.ouaissi@chu-tours.fr
Site Name
Centre Francois Baclesse
Department Name
Radiotherapy
Principal Investigator Name
Mélanie DOS SANTOS
Principal Investigator Email
m.dossantos@baclesse.unicancer.fr
Contact Person Name
Mélanie DOS SANTOS
Site Name
Centre Hospitalier Universitaire De Nimes
Department Name
Digestive surgery
Principal Investigator Name
Michel PRUDHOMME
Principal Investigator Email
drc@chu-nimes.fr
Contact Person Name
Michel PRUDHOMME
Contact Person Email
drc@chu-nimes.fr
Site Name
CHU De Rouen
Department Name
Digestive surgery
Principal Investigator Name
Jean-Jacques TUECH
Principal Investigator Email
jean-jacques.tuech@chu-rouen.fr
Contact Person Name
Jean-Jacques TUECH
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Digestive oncology
Principal Investigator Name
Julien TAIEB
Principal Investigator Email
julien.taieb@aphp.fr
Contact Person Name
Julien TAIEB
Contact Person Email
julien.taieb@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Digestive oncology
Principal Investigator Name
Jean-Baptiste BACHET
Principal Investigator Email
jean-baptiste.bachet@aphp.fr
Contact Person Name
Jean-Baptiste BACHET
Contact Person Email
jean-baptiste.bachet@aphp.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Digestive surgery
Principal Investigator Name
Diane GOERE
Principal Investigator Email
diane.goere@aphp.fr
Contact Person Name
Diane GOERE
Contact Person Email
diane.goere@aphp.fr
Site Name
Centre Hospitalier Et Universitaire De Limoges
Department Name
Oncology radiotherapy
Principal Investigator Name
Pierre CLAVERE
Principal Investigator Email
pierre.clavere@unilim.fr
Contact Person Name
Pierre CLAVERE
Contact Person Email
pierre.clavere@unilim.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Guillaume PIESSEN
Principal Investigator Email
guillaume.piessen@chru-lille.fr
Contact Person Name
Guillaume PIESSEN
Site Name
Institut Bergonie
Department Name
Oncologie digestive
Principal Investigator Name
Simon PERNOT
Principal Investigator Email
s.pernot@bordeaux
Contact Person Name
Simon PERNOT
Contact Person Email
s.pernot@bordeaux
Site Name
Institut Paoli Calmettes
Department Name
Digestive and surgical oncology
Principal Investigator Name
Bernard LELONG
Principal Investigator Email
elongb@ipc.unicancer.fr
Contact Person Name
Bernard LELONG
Contact Person Email
elongb@ipc.unicancer.fr
Site Name
Centre Hospitalier Universitaire De Caen Normandie
Department Name
Digestive surgery
Principal Investigator Name
Arnaud ALVES
Principal Investigator Email
alves-a@chu-caen.fr
Contact Person Name
Arnaud ALVES
Contact Person Email
alves-a@chu-caen.fr
Site Name
Centre Hospitalier Universitaire Reims
Department Name
Digestive surgery
Principal Investigator Name
Koceila LAMINE AMROUN
Principal Investigator Email
lkamroun@chu-reims.fr
Contact Person Name
Koceila LAMINE AMROUN
Contact Person Email
lkamroun@chu-reims.fr
Site Name
Centre Leon Berard
Department Name
Oncologic and digestive surgery
Principal Investigator Name
Aurélien dupre
Principal Investigator Email
aurelien.dupre@lyon.unicancer.fr
Contact Person Name
Aurélien dupre
Site Name
Gie Groupe Hospitalier Paris Saint-Joseph/Vinci
Department Name
Digestive surgery and oncology
Principal Investigator Name
Jérôme LORIAU
Principal Investigator Email
jloriau@gmail.com
Contact Person Name
Jérôme LORIAU
Contact Person Email
jloriau@gmail.com

Sponsor

Primary sponsor

Full Name
Assistance Publique Hopitaux De Paris
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
France

Investigational products

Investigational Product Name
IRINOTECAN
Active Substance
IRINOTECAN HYDROCHLORIDE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Maximum Dose
180 mg/m2
Investigational Product Name
FLUOROURACIL
Active Substance
FLUOROURACIL
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Maximum Dose
2400 mg/m2
Investigational Product Name
OXALIPLATIN
Active Substance
OXALIPLATIN
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Maximum Dose
85 mg/m2
Investigational Product Name
CALCIUM LEVOFOLINATE (PHF00231MIG)
Active Substance
CALCIUM FOLINATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Maximum Dose
200 mg/m2
Investigational Product Name
CALCIUM FOLINATE (PHF00190MIG)
Active Substance
CALCIUM FOLINATE
Modality
Small molecule
Routes Of Administration
INTRAVENOUS INFUSION
Route
Intravenous infusion
Maximum Dose
400 mg/m2
Combination Treatment
Yes

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