Immune Profile and Prognosis of Malignant Liver Tumors With Radiofrequency Ablation (RFA) Therapy (RFA)

Clearing potential intrahepatic metastasis to prevent early recurrence after liver cancer treatment, there are no effective interventions so far. For secondary metastatic cancer, only the lesions visible under ultrasound can be used, one by one for local ablation and chemotherapy, but people may develop new tumor lesions. Therefore, the treatment of potential tumors and recurrent tumors after ablation is a very important clinical issue.

Study Overview

• Status: Completed
• Conditions: Liver Cancer
• Intervention / Treatment: Procedure: Radiofrequency Ablation; Biological: immunotherapy with Nivolumab

Detailed Description

Clearing potential intrahepatic metastasis to prevent early recurrence after liver cancer treatment, there are no effective interventions so far. For secondary metastatic cancer, only the lesions visible under ultrasound can be used, one by one for local ablation and chemotherapy, but people may develop new tumor lesions. Therefore, the treatment of potential tumors and recurrent tumors after ablation is a very important clinical issue. Therefore, this study will include primary liver cancer, as well as secondary metastatic malignant liver cancer, such as colorectal cancer, lung cancer, breast cancer, and other cancers with a high incidence in Chinese patients, and detection of immune cells by surgery, and through various biomarkers to explore its mechanism and efficacy.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Wenshan District
    • Taipei, Wenshan District, Taiwan, 116
      • WanFang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Disease characteristics: Patients with primary or metastatic liver cancer judged by histology
• Age: 20 years old or older
• Life expectation: at least 3 months

• Hematology:

  1. Platelet count: at least 50,000/mm^3
  2. Prothrombin time (PT) or partial thromboplastin time (PTT): no more than 1.5 times the control group
  3. Creatinine: no more than 2.5 mg/dl
• No pregnancy, no rhythm adjuster or other implantable device
• There are no uncontrollable responses to this study
• Other malignant tumors, except for therapeutic non-melanoma skin cancer or cervical cancer 5 years before entering the study inside.
• The number of liver tumors is less than three, the size is less than three centimeters, or the size of a single tumor is less than five centimeters, and those who want to undergo radiofrequency ablation are treated.
• The clotting time is normal and the number of platelets needs to be greater than 50,000, total bilirubin is less than 3 mg/dl, controllable ascites, no extrahepatic metastasis and portal vein invasion, and those who want to undergo radiofrequency ablation.
• The patient refuses or is unable to perform surgery (eg, If the age is too old, for those who want to undergo radiofrequency ablation).
• Patients and their families must fully understand and agree to perform radiofrequency ablation procedures.

Exclusion Criteria:

• There are people with central nervous system metastases.
• Measure lesions only by previous radiotherapy or topical treatment.
• Biliary obstruction did not undergo adequate drainage procedures prior to enrollment.
• White blood cells (WBC) are less than 3,500 / mm3 and absolute neutrophil count (ANC) is less than 1,500 / mm3, platelets less than 100,000 / mm3
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is greater than 5.0 times the upper limit of the normal range (ULN).
• Serum total bilirubin levels are equal to or greater than 2.0 mg / dl.
• Serum creatinine greater than 1.5 mg / dl.
• There are peripheral neuropathies greater than grade 1.
• Concomitant diseases that may accumulate via chemotherapy. For example, active, noncontrolled infection or other activity, non-control Systemic diseases such as congestive heart failure, angina pectoris, respiratory insufficiency, arrhythmia.
• Those who are treated concurrently with other research drugs or other anti-cancer therapies.
• Pregnant or lactating women, or women with fertility potential, unless reliable and appropriate methods of contraception are used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiofrequency Ablation; Malignant Liver Tumors With Radiofrequency Ablation (RFA) Therapy	Procedure: Radiofrequency Ablation; The most commonly used local ablation is radiofrequency ablation. In this operation, a radio frequency probe is used to insert the liver cancer under ultrasound or computer tomography guidance, and then the radio frequency waves generated by the current oscillations locally heat the high temperature, causing the liver cancer cells to die.
Placebo Comparator: Radiofrequency Ablation combine with Nivolumab; Malignant Liver Tumors With Radiofrequency Ablation (RFA) Therapy, and improving immune systems by Nivolumab	Biological: immunotherapy with Nivolumab; After subjects had received radiofrequency ablation for two weeks, they were performed by immunotherapy with Nivolumab 200mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the number of CD8+ T	Analysis of the number of CD8+ T Using PBMC to analyze the number of CD8+ T that is NK, NKT, DC, and Monocyte. Four-time blood draws - 15 ml/each. Week 0- the data of CD8+T before RFA. Week 1- the data of CD8+T after RFA. Week 3- the data of CD8+T after participators received the vaccine which is Nivolumab 200mg in Week 2. Week 6- the data of CD8+T Compare with Week 0 and Week 1 data for analysis the difference of the ability of the immune system. Compare with Week 1 and Week 3 data, if week 3 data is higher than week 1, it means that immunotherapy with Nivolumab has effects to strengthen the immune system. Compare with Week 3 and Week 6 for analysis the effects of immunotherapy with Nivolumab have continued or not. Moreover, analyzed the difference in the immune system between participators who received the vaccine and no received vaccine from week 3 to week 6.	6 weeks

Collaborators and Investigators

• Sponsor: Taipei Medical University WanFang Hospital

Publications and helpful links

General Publications

• Huang AC, Postow MA, Orlowski RJ, Mick R, Bengsch B, Manne S, Xu W, Harmon S, Giles JR, Wenz B, Adamow M, Kuk D, Panageas KS, Carrera C, Wong P, Quagliarello F, Wubbenhorst B, D'Andrea K, Pauken KE, Herati RS, Staupe RP, Schenkel JM, McGettigan S, Kothari S, George SM, Vonderheide RH, Amaravadi RK, Karakousis GC, Schuchter LM, Xu X, Nathanson KL, Wolchok JD, Gangadhar TC, Wherry EJ. T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature. 2017 May 4;545(7652):60-65. doi: 10.1038/nature22079. Epub 2017 Apr 10.
• Dromi SA, Walsh MP, Herby S, Traughber B, Xie J, Sharma KV, Sekhar KP, Luk A, Liewehr DJ, Dreher MR, Fry TJ, Wood BJ. Radiofrequency ablation induces antigen-presenting cell infiltration and amplification of weak tumor-induced immunity. Radiology. 2009 Apr;251(1):58-66. doi: 10.1148/radiol.2511072175. Epub 2009 Feb 27.
• Cui J, Wang N, Zhao H, Jin H, Wang G, Niu C, Terunuma H, He H, Li W. Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma. Int J Cancer. 2014 Jan 15;134(2):342-51. doi: 10.1002/ijc.28372. Epub 2013 Aug 5.
• Napoletano C, Taurino F, Biffoni M, De Majo A, Coscarella G, Bellati F, Rahimi H, Pauselli S, Pellicciotta I, Burchell JM, Gaspari LA, Ercoli L, Rossi P, Rughetti A. RFA strongly modulates the immune system and anti-tumor immune responses in metastatic liver patients. Int J Oncol. 2008 Feb;32(2):481-90.

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2019
• Primary Completion (Actual): July 23, 2020
• Study Completion (Actual): July 23, 2020

Study Registration Dates

• First Submitted: December 16, 2020
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 13, 2021

Study Record Updates

• Last Update Posted (Actual): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: immune cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: N201812053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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