OPTIPRIME

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

Objectives

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

 

LV5FU2

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): 2018

Study Coordinators

Dr. Javier Carrasco

Participating Groups

FFCD

Participating centres

To determine

Protocol summary Protocol summary (synopsis) or full protocol through reserved access
NCT number
EudraCT 2017-001587-38
Interest to participate clinicaltrials@bgdo.org
More info clinicaltrials@bgdo.org