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

Trial Status In preparation
Phase Phase II
Type of cancer Metastatic colorectal adenocarcinoma
Study design

Single-arm, multi-centre


Primary objective:

The primary objective is to evaluate the time to failure of the strategy.

Secondary objectives:

  • 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 8 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.
Inclusion Main 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 <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 Main 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
Treatment schedule

The treatments are not supplied because they are within their indication

Modified FOLFOX6 + Panitumumab

One cycle every 14 days:
Panitumumab: 6 mg/kg IV (D1) duration 60 minutes at the first infusion, then 30 to 60 minutes if the dose is well tolerated. In case of a total dose greater than 1000 mg, administration over 90 minutes for all cycles. Dilution in NaCl 0.9%, 100 mL
Oxaliplatin: 85 mg/m² in Glu 5% or NaCl 0.9% IV (D1) over 2 hours
Folinic acid : 400 mg/m² (or 200 mg/m² if Elvorine) IV over 2 hours, IV (D1) over 2 hours
5FU bolus : 400 mg/m² IV over 10 min
5FU continuous: 2400 mg/m² IV over 46 hours



One cycle every 14 days:
Folinic acid : 400 mg/m² (or 200 mg/m² if Elvorine) IV (D1) over 2 hours
5FU bolus : 400 mg/m² IV over 10 min
5FU continuous: 2400 mg/m² IV over 46 hours

Or (at centre's discretion)

XELODA : 1250 mg/m²/d in two divided doses morning and evening (625 mg/m² morning and 625 mg/m² evening) D1=D15 (without interruption)

Study Period

Recruitment start date (FPI): 2020

Recruitment period: 3 years

Follow-up period: 2 years

Study Coordinators

Dr. Javier Carrasco

Participating Groups


Participating centres
  1. Grand Hôpital de Charleroi
  2. CHC Mont Légia
  3. CHU Namur, Site Godinne
  4. OLV Ziekenhuis Aalst
  5. UCL St-Luc
  6. UZ Antwerpen
  7. Hôpital Ambroise Paré Mons
Protocol summary Protocol summary (synopsis) or full protocol through reserved access
NCT number NCT03584711
EudraCT 2017-001587-38
Interest to participate clinicaltrials@bgdo.org
More info clinicaltrials@bgdo.org