Clinical trial NCT04309747: A Prospective, Multicenter Clinical Trial of Safety and Effectiveness of Nanosecond Knife Ablation for Liver Cancer
Official title: A Prospective, Multicenter Clinical Trial of Safety and Effectiveness of Nanosecond Knife Ablation for Liver Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Liver Cancer
Keywords: nanosecond knife
liver cancer
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
Collaborators: name: Shulan (Hangzhou) Hospital
name: The First Affiliated Hospital of Zhengzhou University
name: First Affiliated Hospital of Xinjiang Medical University
First posted: 2020-03-16
Enrollment: 190
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: To evaluate whether the nanosecond knife can achieve the effectiveness and safety of liver cancer ablation treatment.
Primary purpose: TREATMENT

Brief summary: This is a prospective, multi-center, single-arm clinical trial. Four hospitals with national medical clinical trial institution qualifications are selected as clinical trial centers. Qualified participants will receive nanosecond pulse ablation therapy according to the routine procedures. The results will be recorded according to the requirements of the primary and secondary efficacy indicators. After then, statistical comparisons of effectiveness and safety of the product will be made according to groups.

Detailed description: The prospective, multi-center, single-arm clinical trial is to evaluate whether the nanosecond knife can achieve the effectiveness and safety of liver cancer ablation treatment. Four hospitals with national medical clinical trial institution qualifications are selected as clinical trial centers. This clinical trial requires 190 subjects. Qualified participants will receive nanosecond pulse ablation therapy according to the routine procedures. The results will be recorded according to the requirements of the primary outcome (the effective rate of nanosecond knife ablation for liver cancer) and secondary outcomes (partial response rate, secondary ablation rate, progression-free survival, overall survival rate, quality of life score, alpha-fetoprotein levels, technical success rate, local control rate, complication rate, device Use satisfaction of nanosecond knife ablation for liver cancer). The first 2-month follow-up after the operation, CT, MR, CEUS, liver function, tumor markers were reviewed monthly to observe the lesion necrosis and tumor marker changes. After that, tumor markers, CEUS, or three-phase CT/MRI of liver were examined every 2 to 3 months. After two years, tumor markers, CEUS, or three-phase CT/MRI of liver were examined every 3 to 6 months. After then, statistical comparisons of effectiveness and safety of the product will be made according to groups.

Eligibility criteria: Inclusion Criteria:

1. Liver malignant tumors with clear histopathology and cytology, or liver malignant tumors that meet clinical diagnosis and staging criteria.
2. Age: 18-75 years old, regardless of gender.
3. Liver function: Child-Pugh A or B, or Child C will reach B.
4. No serious heart, lung, brain and other organ dysfunction. Normal or nearly normal blood coagulation function. Prothrombin time does not exceed 50% of the normal control, and platelets are more than 50 × 109 / L.
5. It is usually suitable for single tumor with a maximum diameter of ≤5cm, or the number of tumors of ≤3 and a maximum diameter of ≤3cm.
6. For single tumors \> 5 cm in diameter that cannot be surgically removed, or multiple tumors with a maximum diameter \> 3 cm, local ablation can be used as p palliative comprehensive treatment.
7. According to CT and MRI, there are no macrovascular and bile duct invasions visible by the naked eye.
8. Patients signed informed consent to participate in the trial.

Exclusion Criteria:

1. The lesion of liver cancer is huge or diffuse ;
2. Merged portal vein to secondary branch tumor thrombus or hepatic vein tumor thrombus, invasion of nearby organs or distant metastasis;
3. tumors located on the surface of the liver, of which more than 1/3 tumor size are bare;
4. liver function: Child-pugh C, those could not improve after liver protective treatment;
5. Esophageal (bottom of stomach) varices rupture and bleeding within 1 month before treatment;
6. Uncorrectable coagulation dysfunction and severe haematological abnormalities, who tend to severe bleeding;
7. Refractory large amount of ascites and cachexia;
8. active infection, especially inflammation of the biliary system;
9. Severe failure of major organs such as liver, kidney, heart, lung and brain;
10. Patients with unconsciousness or unable to cooperate with treatment;
11. Subjects could not be followed up and fell off;
12. Those who discontinued treatment, or the case records were incomplete for various reasons, and were determined by researchers to be unable to be evaluated.

Primary outcomes:
measure: Effectiveness analysis
timeFrame: 12 months
Secondary outcomes:
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
measure: Secondary validity analysis
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
References:
citation: Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008 May 21;100(10):698-711. doi: 10.1093/jnci/djn134. Epub 2008 May 13.
citation: Gu YK, Luo RG, Huang JH, Si Tu QJ, Li XX, Gao F. Transarterial embolization ablation of hepatocellular carcinoma with a lipiodol-ethanol mixture. World J Gastroenterol. 2010 Dec 7;16(45):5766-72. doi: 10.3748/wjg.v16.i45.5766.
citation: Bargellini I, Vignali C, Cioni R, Petruzzi P, Cicorelli A, Campani D, De Simone P, Filipponi F, Bartolozzi C. Hepatocellular carcinoma: CT for tumor response after transarterial chemoembolization in patients exceeding Milan criteria--selection parameter for liver transplantation. Radiology. 2010 Apr;255(1):289-300. doi: 10.1148/radiol.09090927.
citation: Fruhling P, Nilsson A, Duraj F, Haglund U, Noren A. Single-center nonrandomized clinical trial to assess the safety and efficacy of irreversible electroporation (IRE) ablation of liver tumors in humans: Short to mid-term results. Eur J Surg Oncol. 2017 Apr;43(4):751-757. doi: 10.1016/j.ejso.2016.12.004. Epub 2017 Jan 11.
citation: Distelmaier M, Barabasch A, Heil P, Kraemer NA, Isfort P, Keil S, Kuhl CK, Bruners P. Midterm Safety and Efficacy of Irreversible Electroporation of Malignant Liver Tumors Located Close to Major Portal or Hepatic Veins. Radiology. 2017 Dec;285(3):1023-1031. doi: 10.1148/radiol.2017161561. Epub 2017 Aug 11.
citation: Bruix J, Sherman M, Llovet JM, Beaugrand M, Lencioni R, Burroughs AK, Christensen E, Pagliaro L, Colombo M, Rodes J; EASL Panel of Experts on HCC. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep;35(3):421-30. doi: 10.1016/s0168-8278(01)00130-1. No abstract available.
citation: Xu M, Xu D, Dong G, Ren Z, Zhang W, Aji T, Zhao Q, Chen X, Jiang T. The Safety and Efficacy of Nanosecond Pulsed Electric Field in Patients With Hepatocellular Carcinoma: A Prospective Phase 1 Clinical Study Protocol. Front Oncol. 2022 Jul 13;12:869316. doi: 10.3389/fonc.2022.869316. eCollection 2022.