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

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

Study Overview

• Status: Recruiting
• Conditions: Refractory Metastatic Colorectal Cancer
• Intervention / Treatment: Device: Radiofrequency electromagnetic field treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pirus Ghadjar, Prof. Dr.; Phone Number: +49 30 450 527318; Email: pirus.ghadjar@charite.de
• Study Contact Backup: Name: Marcus Beck, Dr.; Phone Number: +49 30 450 527318; Email: marcus.beck@charite.de

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charité Universitätsmedizin Berlin
    • Contact: Yvonne Saewe; Phone Number: +49 30 450 527318; Email: yvonne.saewe@charite.de
    • Principal Investigator: Pirus Ghadjar, Prof. Dr.
    • Principal Investigator: Sebastian Stintzing, Prof. Dr.
    • Sub-Investigator: Marcus Beck, Dr.
    • Sub-Investigator: Alexander Hansch, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: TAS-102 and Bevacizumab and radiofrequency electromagnetic field treatment; 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; Radiofrequency electromagnetic field treatment using a carrier frequency of 13.56 MHz; Other Names: mEHT; capacitive hyperthermia; electrohyperthermia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: July 21, 2023
• First Submitted That Met QC Criteria: August 3, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: Live-RF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No