Single-arm, Phase II Trial of Trifluridine/Tipiracil (FTD-TPI), Bevacizumab, and Individualized Radioembolization With 166Ho-microspheres in Refractory Metastatic Colorectal Cancer
Extrahepatic disease progression limits clinical efficacy of individualized radioembolization for patients with refractory metastatic colorectal cancer (mCRC). In the same patient population, trifluridine/tipiracil (FTD-TPI) and bevacizumab lead to disease control and overall survival benefit and may be a radiosensitizer. The purpose of this study is to determine safety, tolerability, and activity of individualized radioembolization with 166Holmium (166Ho)-microspheres combined with FTD-TPI and bevacizumab.
• 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‣ Patients who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of treatment and precluding retreatment with the same agent prior to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