Clinical trial NCT03584711: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: Stop and Go strategy
RAS Wild-type
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2018-07-12
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Single-arm, multi-centre phase II study The primary objective is to evaluate the time to failure of the strategy.

Detailed description: The purpose of the OPTIPRIME phase II non-randomised study is to evaluate the efficacy and tolerability of the combination of FOLFOX plus panitumumab according to a "stop and go" strategy. If disease control is achieved while on induction treatment, oxaliplatin and panitumumab will be stopped after the sixth cycle; a maintenance treatment of fluoropyrimidine alone will be continued. In case of progression during maintenance treatment, oxaliplatin and panitumumab reintroduction loops will take place according to the same regimen (maintenance treatment after six cycles of the reintroduced therapy if disease control is achieved).

Eligibility criteria: 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

Exclusion Criteria:

* - Presence of uncontrolled symptomatic brain metastases
* RAS mutation (KRAS or NRAS 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 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 during symptomatic treatment
* Poorly controlled chronic skin disease
* 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 (example: chemotherapy, targeted therapy, immunotherapy)
* 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
* Persons in custody or under wardship
* Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons

Primary outcomes:
measure: Time to failure of the strategy
timeFrame: Up to 20 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sainte Colombe
country: France
facility: Clinique Trenel
state: Lyon
city: Albi
country: France
facility: Clinique Claude Bernard
city: Amiens
country: France
facility: Hopital Sud
city: Amiens
country: France
facility: Clinique de L'Europe
city: Angers CEDEX 9
country: France
facility: Chu D'Angers
city: Antony
country: France
facility: Hopital Prive D'Antony
city: Arras CEDEX
country: France
facility: Hopital Les Bonnettes
city: Arras
country: France
facility: Centre Marie Curie
city: Bayonne CEDEX
country: France
facility: Ch Cote Basque
city: Beauvais
country: France
facility: Ch de Beauvais
city: Boujan-sur-Libron
country: France
facility: Polyclinique Saint Privat
city: Boulogne-sur-Mer
country: France
facility: Cmco Cote D'Opale
city: Boulogne-sur-Mer
country: France
facility: Hopital Duchenne
city: Brest
country: France
facility: Hopital Morvan - Chu
city: Béziers
country: France
facility: Ch de Beziers Cedex
city: Caen
country: France
facility: Centre Francois Baclesse
city: Cahors
country: France
facility: Ch Cahors
city: Cholet
country: France
facility: Ch de Cholet
city: Châlons-en-Champagne
country: France
facility: Centre Hospitalier General
city: Colmar
country: France
facility: Hopitaux Civils de Colmar
city: Digne-les-Bains
country: France
facility: Service de Medecine
city: Dunkerque CEDEX 01
country: France
facility: CH
city: Flers CEDEX
country: France
facility: Hopital Jacques Monod
city: Fréjus
country: France
facility: Chi de Frejus Saint-Raphael
city: La Chaussee St Victor
country: France
facility: Polyclinique de Blois - 3Eme Etage
city: La Roche-sur-Yon
country: France
facility: Chd Vendee
city: Le Mans CEDEX 9
country: France
facility: Ch Du Mans
city: Lens
country: France
facility: Centre Hospitalier Schaffner
city: Lille
country: France
facility: Chru Hopital Claude Huriez 4Eme Est
city: Lyon
country: France
facility: Ch St Joseph-St Luc
city: Marseille
country: France
facility: Hopital Europeen Marseille
city: Meaux
country: France
facility: Ch de Meaux
city: Mont-de-Marsan
country: France
facility: Hopital Layne
city: Nancy
country: France
facility: Polyclinique de Gentilly
city: Nantes
country: France
facility: Hopital Prive Du Confluent Sas
city: Niort CEDEX
country: France
facility: Ch de Niort - Sce D'Oncologie
city: Paris CEDEX 13
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Paris
country: France
facility: Chu Cochin
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Reims
country: France
facility: Polyclinique de Courlancy
city: Saint-Quentin CEDEX
country: France
facility: Centre Hospitalier
city: Strasbourg
country: France
facility: Clinique Ste Anne
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Tarbes
country: France
facility: Polyclinique de L'Ormeau
city: Toulouse
country: France
facility: Clinique Pasteur
city: Fort-de-France
country: Martinique
facility: Chu de Fort de France
Study officials:
affiliation: Federation Francophone de Cancerologie Digestive
name: Jean-Baptiste Bachet, Pr
role: PRINCIPAL_INVESTIGATOR
References: