FTD-TPI, Bevacizumab, and Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

* Unresectable liver dominant mCRC
* Prior therapy with fluoropyrimidine, oxaliplatin, and irinotecan for the treatment of metastatic colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen

  * Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to progression of disease will also be eligible to enter the study.
  * Patients who refuse oxaliplatin or irinotecan will also be eligible to enter the study.
  * Patients who had received adjuvant chemotherapy and had recurrence during or within 6 months of completion of the adjuvant chemotherapy count the adjuvant therapy as treatment of metastatic colorectal cancer.
* Written informed consent
* Age \>=18 years
* Estimated hepatic tumor replacement ≥ 10% and ≤ 50% of total liver volume Eastern Cooperative Oncology Group performance status 0-1
* Adequate organ function as measured by: WBC ≥ 3.0 x 109/L, platelets ≥ 100 x 109/L, absolute neutrophil count \> 1.5 x 109/L, Hemoglobin (Hb) \> 5 mmol/L (\>8.1 g/dL), eGFR ≥ 35 ml/min, Serum transaminases (AST \& ALT) ≤ 5 x upper limit of normal (ULN), Total bilirubin ≤ ULN, Albumin \> 3 g/dL
* At least one measurable liver lesion according to the PERCIST 1.0

Exclusion Criteria:

* Significant extrahepatic disease, defined as symptomatic extrahepatic disease, more than 10 pulmonary nodules (maximum diameter of each lung metastasis \<20mm), and/or peritoneal carcinomatosis.
* Eligible for ablative local treatment of liver metastases (e.g. surgical resection, ablation)
* Lung shunt \>20 Gy, as calculated using scout dose SPECT/CT
* Absorbed tumor dose \<90 Gy when dosing at a maximum average absorbed normal liver dose
* Other malignancy confounding prognosis
* Receipt of chemotherapy within 28 days prior to study treatment
* Previous or current treatment with radioembolization
* Major surgery within 28 days or incompletely healed surgical incision before starting study therapy
* Any serious comorbidity preventing the safe administration of anti-VEGF antibody treatment. This includes uncontrolled hypertension or treatment with ≥3 antihypertensive drugs, arterial (cerebro)vascular event within the past 6 months, history of severe bleeding, history of GI perforation, or presence of fistulae
* Any serious and/or chronic liver disease preventing the safe administration of radio- embolization
* Uncorrectable extrahepatic deposition of scout dose activity; activity in the falciform ligament, portal lymph nodes and gallbladder is accepted
* Pregnancy or breastfeeding
* Body weight over 150 kg (because of maximum table load)
* Known severe allergy for intravenous contrast fluids
* Participation to another investigational study which may compromise any endpoint of the study