Amplitude Modulated Radiofrequency Electromagnetic Field Treatment Combined With TAS-102 (Lonsurf) and Bevacizumab in Refractory Metastatic Colorectal Cancer

Inclusion Criteria:

* Written informed consent prior to any study procedure
* 18 years or older
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically confirmed colorectal cancer
* Liver metastasis
* Patients received at least two prior regimens of standard chemotherapies and the patient is refractory to or failing these therapies or is unsuitable for the treatment.Standard chemotherapy includes fluoropyrimidine, oxaliplatin, irinotecan,bevacizumab and for patients with KRAS wild-type tumors at least one anti-EGFR monoclonal antibody of cetuximab/panitumumab. Patients with BRAF mutant tumors: BRAF inhibitor, MSI-H patients: Checkpoint-inhibition
* Knowledge of KRAS status (i.e. wild-type or mutant)
* Adequate bone-marrow, liver and renal function:

  1. Hemoglobin value of ≥9.0 g/dL.
  2. Absolute neutrophil count of ≥1,500/mm3
  3. Platelet count ≥100,000/mm3 (IU: ≥100 × 109/L).
  4. Total serum bilirubin of ≤1.5 mg/dL
  5. Aspartate aminotransferase and alanine aminotransferase

     ≤3.0 × upper limit of normal (ULN); if liver function abnormalities are due to underlying Liver metastasis, AST and ALT ≤5 × ULN.
  6. Serum creatinine of ≤1.5 mg/dL.
* Patient is able to take medications orally
* Women of childbearing potential with negative pregnancy test and agreement for adequate birth control if conception is possible

Exclusion Criteria:

* Significant extrahepatic metastasis
* Previous treatment with TAS 102
* Serious illness other than colorectal cancer or serious medical condition:

  1. Other concurrently active malignancies excluding malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment.
  2. Known brain metastasis or leptomeningeal metastasis.
  3. Active infection (ie, body temperature ≥38°C due to infection).
  4. Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks
  5. Intestinal obstruction, pulmonary fibrosis, renal failure, liver failure, or cerebrovascular disorder
  6. Uncontrolled diabetes.
  7. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA III/IV)
  8. Gastrointestinal hemorrhage.
  9. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C.
  10. Patients with autoimmune disorders or history of organ transplantation who require immunosuppressive therapy.
  11. Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results.
* Radiofrequency treatment technically not possible (e.g. larger metal implants)
* Cardiac pacemakers/ICD
* Patient not able for supine positioning (e.g. due to pain)