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

Phase 2

Active, not recruiting

• Conditions: Metastatic Colorectal Cancer
• Interventions: Combination Product: FOLFOX + panitumumab

• Registration Number: NCT03584711
• Lead Sponsor: Federation Francophone de Cancerologie Digestive

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).

Study Timeline

• Study Start: 2018-04-26
• Study First Submitted: 2018-06-19
• Study First Submitted QC: 2018-06-29
• Study First Posted: 2018-07-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-05
• Last Update Posted: 2024-07-08
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 118

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FOLFOX + panitumumab	FOLFOX + panitumumab	1 cylce every 14 days : Panitumumab : 6 mg/kg en IV (J1) during 60 minutes for 1st infusion followed by 30 to 60 minutes Oxaliplatine : 85 mg/m² inG5% orNaCl 0.9% in IV (D1) during 2 hours Acide folinique : 400 mg/m² (or200 mg/m² if Elvorine) in IV (D1) 5Fu bolus : 400 mg/m² in IV 5FU continu : 2400 mg/m² in IV during 46 hours LV5FU2 : 1 cycle every 14 days Acide folinique : 400 mg/m² (or 200 mg/m² ifElvorine) in IV (D1) during 2 hours 5FU bolus : 400 mg/m² in IV 5FU continu : 2400 mg/m² in IV during 46 hours

Primary Outcome Measures

Name	Time	Method
Time to failure of the strategy	Up to 20 months	Time to strategy Failure is defined as the time from date of inclusion to strategy failure (Radiological progression under treatment or death or definitive treatment discontinuation or recurrence after curative surgery with or without adjuvant treatment)

Trial Locations

Locations (45)

Ch Cote Basque; 🇫🇷 Bayonne CEDEX, France

Hopital Jacques Monod; 🇫🇷 Flers CEDEX, France

Chi de Frejus Saint-Raphael; 🇫🇷 Fréjus, France

Ch Du Mans; 🇫🇷 Le Mans CEDEX 9, France

Centre Hospitalier Schaffner; 🇫🇷 Lens, France

Ch St Joseph-St Luc; 🇫🇷 Lyon, France

Hopital Layne; 🇫🇷 Mont-de-Marsan, France

Polyclinique de Gentilly; 🇫🇷 Nancy, France

Hopital Prive Du Confluent Sas; 🇫🇷 Nantes, France

Ch de Niort - Sce D'Oncologie; 🇫🇷 Niort CEDEX, France

Groupe Hospitalier Pitie-Salpetriere; 🇫🇷 Paris, France

Clinique Pasteur; 🇫🇷 Toulouse, France

Chu de Fort de France; 🇲🇶 Fort-de-France, Martinique

Chru Hopital Claude Huriez 4Eme Est; 🇫🇷 Lille, France

Centre Hospitalier; 🇫🇷 Saint-Quentin CEDEX, France

Clinique Ste Anne; 🇫🇷 Strasbourg, France

Clinique Trenel; 🇫🇷 Sainte Colombe, Lyon, France

Clinique Claude Bernard; 🇫🇷 Albi, France

Hopital Sud; 🇫🇷 Amiens, France

Hopital Prive D'Antony; 🇫🇷 Antony, France

Clinique de L'Europe; 🇫🇷 Amiens, France

Chu D'Angers; 🇫🇷 Angers CEDEX 9, France

Hopital Les Bonnettes; 🇫🇷 Arras CEDEX, France

Centre Marie Curie; 🇫🇷 Arras, France

Ch de Beauvais; 🇫🇷 Beauvais, France

Polyclinique Saint Privat; 🇫🇷 Boujan-sur-Libron, France

Cmco Cote D'Opale; 🇫🇷 Boulogne-sur-Mer, France

Hopital Morvan - Chu; 🇫🇷 Brest, France

Hopital Duchenne; 🇫🇷 Boulogne-sur-Mer, France

Ch de Beziers Cedex; 🇫🇷 Béziers, France

Ch Cahors; 🇫🇷 Cahors, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Ch de Cholet; 🇫🇷 Cholet, France

Hopitaux Civils de Colmar; 🇫🇷 Colmar, France

Centre Hospitalier General; 🇫🇷 Châlons-en-Champagne, France

Service de Medecine; 🇫🇷 Digne-les-Bains, France

CH; 🇫🇷 Dunkerque CEDEX 01, France

Polyclinique de Blois - 3Eme Etage; 🇫🇷 La Chaussee St Victor, France

Chd Vendee; 🇫🇷 La Roche-sur-Yon, France

Hopital Europeen Marseille; 🇫🇷 Marseille, France

Ch de Meaux; 🇫🇷 Meaux, France

Polyclinique de Courlancy; 🇫🇷 Reims, France

Chu Cochin; 🇫🇷 Paris, France

Polyclinique de L'Ormeau; 🇫🇷 Tarbes, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France