Clinical Trials Register

Summary
EudraCT Number:	2017-001587-38
Sponsor's Protocol Code Number:	OPTIPRIME
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-06-26
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2017-001587-38

A.3

Full title of the trial

A phase II study evaluating FOLFOX + panitumumab according to a "stop and go" strategy with a reintroduction loop after progression on fluoropyrimidine as maintenance treatment, as the first line in patients with metastatic colorectal adenocarcinoma without a RAS mutation

Etude de phase II évaluant le FOLFOX + PANITUMUMAB selon une stratégie de "stop and go" avec boucle de ré-introduction après progression sous fluoropyrimidine en traitement d'entretien, en 1ère ligne chez des patients atteints d'un adénocarcinome colorectal métastatique sans mutation RAS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Clinical study assessing antibody adding (panitumumab) to a chemotherapy of reference in metastatic colorectal cancer (FOLFOX), following a strategy with a switch between full treatment and light treatment.

Etude clinique évaluant l’ajout d’un anticorps (le panitumumab) à une chimiothérapie de référence dans le cancer colorectal métastatique (le FOLFOX), en suivant un schéma alternant un traitement complet avec une phase de traitement allégé.

A.3.2

Name or abbreviated title of the trial where available

OPTIPRIME

A.4.1

Sponsor's protocol code number

OPTIPRIME

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fédération Francophone de Cancérologie Digestive
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Belgian Group of Digestive Oncology (BGDO)
B.4.2	Country	Belgium
B.4.1	Name of organisation providing support	FFCD itself
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Belgian Group of Digestive Oncology (BGDO)
B.5.2	Functional name of contact point	Clinical Trial Coordinator
B.5.3	Address:
B.5.3.1	Street Address	Leuvensesteenweg 643
B.5.3.2	Town/ city	Zaventem
B.5.3.3	Post code	1930
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+32478810427
B.5.5	Fax number	000
B.5.6	E-mail	i.debruyne@bgdo.org

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Fluorouracil Accord Healthcare 50 mg/ml, solution pour injection ou perfusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord Healthcare B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FLUOROURACIL
D.3.9.3	Other descriptive name	FLUOROURACIL
D.3.9.4	EV Substance Code	SUB07721MIG
D.3.10	Strength
D.3.10.3	Concentration number	50 mg/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xeloda 150 mg comprimés pelliculés.
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPECITABINE
D.3.9.3	Other descriptive name	CAPECITABINE
D.3.9.4	EV Substance Code	SUB12474MIG
D.3.10	Strength
D.3.10.3	Concentration number	150 mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xeloda 500 mg comprimés pelliculés.
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CAPECITABINE
D.3.9.3	Other descriptive name	CAPECITABINE
D.3.9.4	EV Substance Code	SUB12474MIG
D.3.10	Strength
D.3.10.3	Concentration number	500 mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ELOXATIN 5 mg/ml solution à diluer pour perfusion
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI BELGIUM
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	OXALIPLATIN 5 mg/ml
D.3.9.1	CAS number	61825-94-3
D.3.9.3	Other descriptive name	OXALIPLATIN 5 mg/ml
D.3.9.4	EV Substance Code	SUB09490MIG
D.3.10	Strength
D.3.10.3	Concentration number	5 mg/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 5
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vectibix 20 mg/mL solution à diluer pour perfusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Amgen Europe B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PANITUMUMAB
D.3.9.1	CAS number	339177-26-3
D.3.9.3	Other descriptive name	PANITUMUMAB
D.3.9.4	EV Substance Code	SUB25390
D.3.10	Strength
D.3.10.3	Concentration number	20 mg/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Anticorps IgG2 entièrement humain
D.IMP: 6
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Elvorine 25 mg/2,5 ml solution injectable Elvorine 50 mg/5 ml solution injectable
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer SA, Bruxelles
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ELVORINE 50 mg/ml
D.3.9.3	Other descriptive name	CALCIUM LEVOFOLINATE
D.3.9.4	EV Substance Code	SUB06054MIG
D.3.10	Strength
D.3.10.3	Concentration number	50 mg/ml
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

metastatic colorectal adenocarcinoma without a RAS mutation

adénocarcinome colorectal métastatique sans mutation RAS

E.1.1.1

Medical condition in easily understood language

patient with a metastatic colorectal cancer

Patient présentant un cancer colorectal métastatique

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate the disease control duration

L’objectif principal est d’évaluer le temps jusqu'à l'échec de la stratégie

E.2.2

Secondary objectives of the trial

- Progression-free survival (PFS) 1 (first radiological progression or death)
- Successive periods of progression-free survival
- The best tumour response during treatment, the early response rate at 6 weeks and the maximum depth of response, evaluated according to the RECIST V1.1 criteria according to the investigator and centralised imaging review
- Overall survival
- Quality of life of patients (EORTC QLQ-C30)
- Time to final deterioration of the overall health score
- Safety profile, particularly in regard to skin toxicity events (acneiform rash, xeroderma, paronychia)
- The predictive value of early evolution (at two weeks) of the circulating tumour DNA level correlated with the RECIST 1.1 response rate and the PFS 1
- The appearance of resistance mutations and clonal selection through analysis of circulating tumour DNA every two months.

- La survie sans progression (SSP) 1 (1ère progression radiologique ou décès)
- Les survies sans progression successives
- La meilleure réponse tumorale sous traitement, le taux de réponse précoce à 6 semaines et la profondeur de réponse maximale, évalués selon les critères RECIST V1.1 selon l’investigateur et selon la relecture centralisée des imageries
- La survie globale
- La qualité de vie des patients (EORTC QLQ-C30)
- Le temps jusqu’à détérioration définitive du score de santé globale
- Le profil de sécurité, en particulier concernant les toxicités cutanées (rash acnéiforme, xérose, paronychie)
- La valeur prédictive de l’évolution précoce (à 2 semaines) du taux d’ADN tumoral circulant avec corrélation avec le taux de réponse RECIST 1.1 et la SSP 1
- L’apparition de mutations de résistance et de sélection clonale par l’analyse de l’ADN tumoral circulant tous les deux mois.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Circulating tumour DNA study as potential marker of disease (analyses of circulating tumour DNA level and genetic alterations associated to therapy resistance). Genetic alterations associated to therapy resistance would also be studied from tumor samples.

Etude de l'ADN tumoral circulant comme marqueur pronostique de la maladie (étude du taux d'ADN tumoral circulant et des altérations génétiques en lien avec une résistance au traitement). La recherche de biomarqueurs prédictifs de l’efficacité de la combinaison FOLFOX + panitumumab en 1ère ligne thérapeutique sera également réalisée à partir d'échantillons tumoraux.

E.3

Principal inclusion criteria

- Histologically proven colorectal adenocarcinoma without RAS mutation
- Confirmed, non-resectable metastatic disease (Stage IV)
- No prior chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months
- At least one measurable metastasis according to the RECIST v1.1 criteria
- Age ≥ 18 years
- WHO ≤ 2
- Neutrophils ≥ 1500 /mm3, platelets ≥ 100 000/mm3, Hb ≥ 9 g/dL
- Creatinine clearance ≥ 50 mL/min according to the MDRD formula
- Serum bilirubin ≤ 25 µmol/L, AST, ALT, Alk Phos ≤ 2.5 x ULN or ≤ 5 x ULN in case of liver metastases
- PT ≥ 60%, albumin ≥ 25g/L
- Estimated life expectancy ≥ 3 months
- Patient affiliated to a social security scheme
- Patient informed and informed consent form signed

- Adénocarcinome colorectal histologiquement prouvé sans mutation RAS
- Maladie métastatique confirmée et non résécable (Stade IV)
- Pas de chimiothérapie antérieure exceptée la chimiothérapie péri-opératoire ou adjuvante arrêtée depuis plus de 12 mois
- Au moins une lésion mesurable métastatique selon les critères RECIST 1.1
- Age ≥18 ans
- OMS ≤ 2
- PNN ≥ 1500 /mm3, plaquettes ≥ 100 000/mm3, Hb ≥ 9 g/dL
- Clairance de la créatinine ≥ 50 mL/min selon formule MDRD
- Bilirubinémie ≤ 25 µmol/L, ASAT, ALAT, PAL ≤ 2.5 x LSN ou ≤ 5 x LSN en cas de métastases hépatiques
- TP ≥ 60%, albumine ≥ 25g/L
- Esperance de vie estimée ≥ 3 mois
- Patient affilié au régime de sécurité sociale
- Information du patient et signature du consentement éclairé

E.4

Principal exclusion criteria

- Presence of uncontrolled symptomatic brain metastases
- RAS mutation (KRAS or NRAS mutation) or BRAF mutation
- Patient taking warfarin. If treated with anticoagulant at the indicated effective dose, this must be replaced with low molecular weight heparin before inclusion
- Known total or partial dehydropyrimidine dehydrogenase (DPD) deficiency
- Peripheral neuropathy ≥ 1 (NCI CTCAE v4.0)
- Patient with interstitial pneumonitis or pulmonary fibrosis
- History of chronic diarrhoea or inflammatory disease of the colon or rectum, or obstruction or sub-obstruction non-resolved during symptomatic treatment
- chronic skin disease not controlled
- Treatment with sorivudine or its chemically related analogues such as brivudine
- Association with the yellow fever vaccine
- Patient included simultaneously in another therapeutic trial with an experimental molecule (example: chemotherapy, targeted therapy, immunotherapy)
- Any known specific contraindication or allergy to the medicinal products used in the study
- Patient simultaneously included in another clinical trial involving an investigational drug
- Arterial hypertension not controlled by medical treatment (Systolic BP ≥ 160 mmHg end/or diastolic BP ≥ 90 mmHg)
- Any progressive pathology not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure
- The following conditions in the 6 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischaemic attack
- Patient who has received a transplant, is seropositive for HIV, hepatitis B or hepatitis C or has other immunodeficiency syndromes
- History of malignant pathologies during the past 5 years except basal cell carcinoma of the skin or cervical carcinoma in situ, properly treated
- QT/QTc interval > 450 msec for men and > 470 msec for women
- K+ < LNL, Mg2+ < LNL, Ca2+ < LNL
- Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age who have not had a pregnancy test. Women of childbearing potential should agree to use a method of contraception during treatment of the trial and at least 4 months after discontinuation of oxaliplatin therapy, at least 2 months after discontinuation of panitumumab therapy and at least 30 days after discontinuation of 5-fluorouracil or capecitabine. Men must agree to use a method of contraception during treatment and at least 6 months after stopping oxaliplatin therapy and at least 3 months after stopping 5-fluorouracil or capecitabine.
- Persons in custody or under wardship
- Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons

- Présence de métastase(s) cérébrale(s) symptomatiques non contrôlées
- RAS muté (KRAS ou NRAS muté)
- Patient prenant de la coumadine. En cas de traitement anticoagulant à dose efficace indiqué, un relai par héparine de bas poids moléculaire doit être réalisé avant inclusion
- Déficit connu en DPD
- Neuropathie périphérique ≥ 1 (NCI CTCAE v4.0)
- Patient présentant une pneumopathie interstitielle ou une fibrose pulmonaire
- Antécédent de diarrhée chronique ou de maladie inflammatoire du côlon ou du rectum, ou d’occlusion ou de sub-occlusion non résolues sous traitement symptomatique
- Pathologie cutanée chronique mal contrôlée
- Toute contre-indication spécifique ou allergie connue aux médicaments utilisés dans l’étude
- Traitement par la sorivudine ou ses analogues chimiquement apparentés telle que la brivudine
- Association avec le vaccin contre la fièvre jaune
- Patient inclus simultanément dans un autre essai thérapeutique avec une molécule expérimentale (exemple : chimiothérapie, thérapie ciblée, immunothérapie)
- Hypertension artérielle non contrôlée par un traitement médical (PAS ≥ 160 mmHg et/ou PAD ≥90 mmHg)
- Toute affection évolutive non équilibrée au cours des 6 derniers mois : insuffisance hépatique, insuffisance rénale, insuffisance respiratoire
- Atteintes suivantes au cours des 6 mois précédant l’inclusion : infarctus du myocarde, angine de poitrine sévère/instable, pontage aorto-coronarien, insuffisance cardiaque congestive de classe NYHA II, III ou IV, accident vasculaire cérébral ou accident ischémique transitoire
- Patient transplanté, séropositif pour VIH, hépatite B ou hépatite C, ou autres syndromes d’immunodéficience
- Antécédent de pathologies malignes dans les 5 dernières années à l’exception du carcinome basocellulaire de la peau ou du carcinome in situ du col utérin correctement traités
- Intervalle QT/QTc > 450 msec pour les hommes et > 470 msec pour les femmes
- K+ < LIN, Mg2+ < LIN, Ca2+ < LIN
- Absence de contraception efficace chez les patients (homme ou/et femme) en âge de procréer, femme enceinte ou allaitante, femme en âge de procréer n’ayant pas réalisé de test de grossesse Les femmes en âge de procréer doivent accepter d’utiliser une méthode de contraception pendant le traitement de l’essai et au moins 4 mois après l’arrêt du traitement par oxaliplatine , au moins 2 mois après l’arrêt du traitement par panitumumab et au moins 30 jours après l’arrêt du 5-fluorouracile ou de capécitabine. Les hommes doivent accepter d’utiliser une méthode de contraception pendant le traitement et au moins 6 mois après l’arrêt du traitement par oxaliplatine et au moins 3 mois après l’arrêt du 5-fluorouracile ou de capécitabine.
- Personne privée de liberté ou sous tutelle
- Impossibilité de se soumettre au suivi médical de l'essai pour des raisons géographiques, sociales ou psychiques

E.5 End points

E.5.1

Primary end point(s)

the primary endpoint is the disease control duration

temps jusqu'à l'échec de la stratégie

E.5.1.1

Timepoint(s) of evaluation of this end point

2 years after last patient registration

2 ans après le dernier patient inclus

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

2 years after last patient registration

2 ans après le dernier patient inclus

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.1.7.1

Other trial design description

Monobras

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

stratégie de traitement classique sous FOLFOX (sans stop and go)

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

Dernière visite du dernier patient inclus dans l'étude

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

The study treatment will be discontinued in the event of:
-Disease progression on modified FOLFOX 6 + panitumumab
-Decision of the investigator
-Major toxicity requiring discontinuation of the treatment
-A serious or unexpected event requiring the discontinuation of the study treatment
-Patient refusal or withdrawal of consent
In all cases of treatment discontinuation, follow-up of the patient will continue according to recommendations of "Thesaurus National de Cancérologie Digestive"

Les patients seront suivis et traités dès lors qu'ils rentrent en échec de la stratégie selon les recommandations du Thesaurus National de Cancérologie Digestive

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2019-08-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-08-05

P. End of Trial
P.	End of Trial Status	Ongoing

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