Holmium-166 TARE in Liver Limited Unresectable Colorectal Cancer Patients

Inclusion Criteria

• •Written informed consent to study procedures;
• •Age ≥18 years;
• •Histologically proven diagnosis of colorectal adenocarcinoma, with or without primary tumour in situ;
• •Liver-only disease at radiological exams involving less than 50% of liver volume;
• •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2;
• •Patients with partial response or stable disease according to RECIST 1.1 criteria deemed unresectable after 6-12 cycles of induction first-line chemotherapy;
• •Life expectancy of at least 12 weeks;
• •Hematopoietic function: absolute neutrophil count ≥ 1,500/mm3; platelet count
• •≥100,000/mm3; haemoglobin level ≥ 9 g/dL;
• •Liver function: total bilirubin ≤ 1.5 times upper limit of normal (ULN); alkaline phosphatase
• •≤ 5 times ULN; AST ≤ 5 times ULN;
• •Renal function: creatinine clearance \> 50 mL/min or serum creatinine 1.5 x UNL; no renal disease that would preclude study treatment or follow-up;
• •Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient;
• •Subjects and their partners must be willing to avoid pregnancy during the trial. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as outlined in Section 7.5 - Contraception, starting during study screening visit throughout the study period up to 180 days after the last dose of chemotherapy Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject;
• •Will and ability to comply with the protocol
• •RAS/BRAF wild-type and left sided primary tumor
• •First-line induction chemotherapy regimen permitted up to 6-12 cycles with:
• •FOLFOX or FOLFIRI + anti-EGFR (cetuximab or panitumumab). Patients who interrupted anti-EGFR target therapy during induction phase due to toxicity or other reasons, candidate to maintenance with fluoropyridine alone therapy can be enrolled.
• •RAS mutated and/or right-sided primary tumor
• •First-line induction chemotherapy regimen admitted up to 6-12 cycles with:
• •FOLFOX/FOLFIRI/XELOX + bevacizumab or FOLFOXIRI + bevacizumab. Patients who interrupted bevacizumab during induction phase due to toxicity or other reasons, candidate to maintenance with fluoropyridine alone therapy can be enrolled.