Randomized, Multicenter Phase II Study of Monoclonal FOLFOX6m + mAb Alone or in Combination With Liver Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease Limited to the Liver With Poor Prognosis
Randomized, Multicenter Phase II Study of Monoclonal FOLFOX6m + mAb Alone or in Combination With Liver Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease Limited to the Liver With Poor Prognosis
Non-commercial, prospective, randomized, multicenter, national, phase II, open-label comparative clinical trial.
The patients will be randomized in a 1: 1 ratio in two arms:
Control arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab Experimental arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.
The main objective is to evaluate the radiological objective response rate according to the RECIST version 1.1 criteria at 6 months. Secondary objectives include: Evaluate overall survival, progression-free survival (PFS), safety profile, hepatic PFS, R0 liver surgery rate.
Hepatic intra-arterial therapy (TACE) with irinotecan has been used in several prospective studies demonstrating an acceptable toxicity profile. Two randomized phase II studies have evaluated the efficacy of TACE with irinotecan compared to conventional chemotherapy in metastatic colon cancer. A second-line treatment study demonstrated an increase in PFS in the TACE versus FOLFIRI treatment arm.
A prospective open, randomized, multicenter phase II study is proposed that will include patients with liver metastases of colorectal origin with poor prognostic criteria.
LIFEPEARLS® is a CE marked medical device consisting of microspheres for use in chemoembolization. The device uses 100 +/- 50 micron microspheres of hydrogel into which chemotherapeutic agents are loaded and delivered into the hepatic artery to treat liver tumors. This device allows the continuous release of irinotecan in liver tumors causing a specific necrosis. The penetration of irinotecan into the tumor tissue is deeper thanks to the microspheres, avoiding proximal occlusion of the vessels supplying the tumor.
Systemic treatment will be administered according to the usual guidelines:
-FOLFOX6m for 6 months + monoclonal Ab (cycles are repeated every 15 days) Premedication: Dexamethasone 20 mg IV + ondansetron 8mg IV
The dose of FOLFOX will be:
Leucovorin: 400 mg / m2 IV over 15 minutes on day 1 of each cycle. Fluorouracil (5-FU): 400mg / m2 IV bolus (15 min) followed by continuous IV infusion for 46 h of 2,400 mg / m2 on day 1 of each cycle.
Oxaliplatin 85 mg / m2 IV over 120 minutes on cycle day 1. In case of RAS wt colorectal cancer administer anti-EGFR together with FOLFOX6m, and in case of mutated RAS colorectal cancer administer Bevacizumab together with FOLFOX6m.
In the combination arm of systemic chemotherapy with IRINOPEARL, in the 2nd and 4th cycles, chemotherapy will be replaced by treatment with hepatic chemoembolization with IRINOPEARL.
The disease will be evaluated by CT or MRI at baseline and every 12 weeks until progression according to RECIST 1.1 criteria.
Inclusion Criteria:
Patients aged ≥ 18 years.
Patients with colorectal cancer and exclusive liver metastases with poor prognostic criteria,> 3 lesions and / or size> 5 cm. Patients with a diagnosis of liver metastases with synchronous presentation or with a disease-free interval may be included. If the primary tumor has not been resected, it must be clinically stable.
Measurable disease following RECIST version 1.1 criteria
Adequate bone marrow function, according to:
Adequate liver function, according to:
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
Patients capable of understanding the information and giving their written informed consent to participate in the study
Women of childbearing potential must commit to sexual abstinence or use of barrier contraceptive methods during the study and must have a negative pregnancy test.
Exclusion Criteria: