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): 2020
Recruitment period: 3 years
Follow-up period: 2 years
|
Study Coordinators |
Dr. Javier Carrasco
|
Participating Groups |
FFCD
|
Participating centres |
- Grand Hôpital de Charleroi
- CHC Mont Légia
- CHU Namur, Site Godinne
- OLV Ziekenhuis Aalst
- UCL St-Luc
- UZ Antwerpen
- 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 |