Colorectal Cancer Metastatic
Conditions
Brief summary
National trial, multicenter, randomized, phase II comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy (CT) to systemic chemotherapy alone in patients with liver-only colorectal metastases (CRLM) considered still non resectable after at least two months of systemic induction chemotherapy.
Detailed description
to compare the efficacy of CT intensification combining hepatic arterial infusion(HAI) oxaliplatin plus IV FOLFIRI plus targeted therapy (anti-epidermal growth factor receptor (EGFR) or bevacizumab) to conventional systemic CT alone plus targeted therapy (anti-EGFR or antiangiogenic antibody), in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after systemic induction CT in terms of conversion to complete (R0 R1) resection (or ablation) rate (CRR).
Interventions
DRUGOxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil
Oxaliplatin 100 mg/m² infusion in 2 hours, Cetuximab 500mg/m² infusion in 2 hours, Bevacizumab 5 mg/kg infusion in 30 minutes, Panitumumab 6 mg/kg, Irinotecan 180 mg/m² over 90 minutes to begin 30 minutes after folinic acid infusion is started, Leucovorin 400 mg/m² infusion in 2 hours, 5-Fluorouracil 2400 mg/m² infusion continuous in 46h
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed colorectal cancer (CRC), and radiologic or histologic proof of CRLM not amenable to a curative intent-treatment. 2. At least two months of prior induction systemic CT with oxaliplatin and/or irinotecan combined with a fluoropyrimidine combined or not to a targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) for metastatic disease (patients ending their adjuvant chemotherapy after primary tumor resection since more than 6 months should also have received first-line chemotherapy for metastatic disease). Further systemic chemotherapy lines are allowed. 3. Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria): * Upfront R0/R1 resection of all CRLM (that leaves at least two adequately perfused and drained segments) is not possible * and/or metastases in contact with major vessels of the remnant liver which would require resection of the vessel for an R0 resection (i.e., tumor involvement of main portal right and left portal veins, of the three main hepatic veins, or of the retrohepatic vena cava) * and/or documented progressive disease on imaging (according to the RECIST v1.1) or doubling of serum levels of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9) following ≥2 months of induction CT 4. At least one measurable liver metastasis according to the RECIST v1.1 5. Age ≥18 years 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 7. Normal liver function, i.e. bilirubin \<1.5 times the upper limit of normal values (ULN), aminotransferases \<5 ULN, alkaline phosphatase \<5 ULN 8. International normalized ratio (INR) \<1.5 ULN 9. Neutrophils \>1500/mm³, platelets \>100 000/mm³, hemoglobin \>9 g/dL (transfusion allowed) 10. Calculated creatinine clearance \>50 mL/min (Cockcroft and Gault formula) 11. Informed consent signed by the patient or his/her legal representative 12. Patient affiliated to a social security regimen 13. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 6 months after the last dose of study drug. 14. Uracilemia \<16 ng/ml
Exclusion criteria
1. Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review. 2. Definitive anatomical contraindication to complete surgical resection (any of the following criteria): * More than two lesions in all liver segments * Bilobar liver metastasis and more than three lesions \>3 cm in the hepatic lobe the least affected (i.e. the future remnant liver) * Bilobar liver metastasis and disease liver extend \>50% 3. Extrahepatic tumor disease (except ≤3 lung nodules \<10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms) 4. Patient with contraindication for trial drugs (investigators have to refer to drugs SmPC); contraindication limited to targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM | 6 months | Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM confirmed by a systematic review of the surgical and pathological report by an independent committee blind to the treatment received |
Countries
France
Outcome results
None listed