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

Study Overview
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Brief Summary
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Combined chemotherapy and radiofrequency electromagnetic field treatment for patients with liver dominant refractory metastatic colorectal cancer

Detailed Description
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Charité Universitätsmedizin Berlin is currently the only German University Hospital with an available capacitive radiofrequency electromagnetic field treatment device. While there is only data available regarding the low toxicity profile of radiofrequency electromagnetic field treatment for various regions of the body including the abdomen there is no data available on the combined effect of TAS-102 and Bevacizumab and radiofrequency electromagnetic field treatment. The investigators aim to conduct a feasibility trial and plan to compare the results with data of a prospective trial with a comparable patient population.

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

Conditions
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Refractory Metastatic Colorectal Cancer

Intervention / Treatment
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* Device: Radiofrequency electromagnetic field treatment


Participation Criteria
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Eligibility Criteria
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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: Hemoglobin value of ≥9.0 g/dL. Absolute neutrophil count of ≥1,500/mm3 Platelet count ≥100,000/mm3 (IU: ≥100 × 109/L). Total serum bilirubin of ≤1.5 mg/dL 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. 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: Other concurrently active malignancies excluding malignancies that are disease free for more than 5 years or carcinoma-in-situ deemed cured by adequate treatment. Known brain metastasis or leptomeningeal metastasis. Active infection (ie, body temperature ≥38°C due to infection). Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks Intestinal obstruction, pulmonary fibrosis, renal failure, liver failure, or cerebrovascular disorder Uncontrolled diabetes. Myocardial infarction within the last 12 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA III/IV) Gastrointestinal hemorrhage. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C. Patients with autoimmune disorders or history of organ transplantation who require immunosuppressive therapy. 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS-102 and Bevacizumab and radiofrequency electromagnetic field treatment<br>Each treatment cycle with TAS-102 will be 28 days in duration. One treatment cycle consists of the following: Days 1: Bevacizumab (5 mg/m2/dose) intravenous. Days 1 through 5: TAS-102 (35 mg/m2/dose) orally 2 times daily with the first dose administered in the morning of Day 1 of each cycle and the last dose administered in the evening of Day 5. Days 6 through 7: Recovery Days 8 through 12: TAS-102 (35 mg/m2/dose) orally 2 times daily with the first dose administered in the morning of Day 8 of each cycle and the last dose administered in the evening of Day 12. Days 13 through 28: Recovery Days 15: Bevacizumab (5 mg/m2/dose) intravenously. Radiofrequency electromagnetic field treatment using the EHY-2030 device starts within the first week of systemic therapy 2 times weekly (60 min each) with an interval of at least 48h. A modulated electric field with a carrier radiofrequency 13.56 MHz will be generated. | Device: Radiofrequency electromagnetic field treatment<br>* Radiofrequency electromagnetic field treatment using a carrier frequency of 13.56 MHz<br>* Other names: electrohyperthermia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | (≥ partial response) | Through study completion, an average of 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | Through study completion, an average of 6 months | 
| OS | Overall survival | Through study completion, an average of 1 year | 
| QoL | European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 | During 3 years of trial conduction | 
| QoL | European Organisation for Research and Treatment of Cancer (EORTC) QLQ-LMC21 | During 3 years of trial conduction | 
| Anxiety and depression | Hospital Anxiety and Depression Scale (HADS-D) | During 3 years of trial conduction | 
| Acute and late toxicity | CTCAE version 5 | During 3 years of trial conduction |