RFA or Surgical Resection Combined With Neo-MASCT for Primary HCC: a Phase II Trial

Immunotherapy Clinical Trial

— RAMEC  

Official title:

Radiofrequency Ablation or Surgical Resection Combined With Neo-MASCT for Primary Hepatocellular Carcinoma: a Randomised, Multicentre Phase II Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03067493
• Other study ID #: HCC008
• Status: Recruiting
• Phase: Phase 2
• Start date: July 25, 2017
• Est. completion date: March 31, 2023

Study information

• Verified date: January 2022
• Source: Sun Yat-sen University
• Contact: Ming Kuang, Ph.D.
• Phone: 008687755766
• Email: kuangm[@]mail.sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RAMEC is a phase II, multi-center, randomized trial with a safety test. There will be a safety test to establish the safety and tolerability of Neo-MASCT treatment and assess the immune response to the treatment.The randomized trial will assess DFS and immune response.

Description:

The safety test will recruit 10 patients. Following registration they will receive 3 cycles of Neo-MASCT treatment. Patients will be seen at week 1, week 2 and week 4 of every cycle. Following the safety test, 98 patients will be randomized to the trial across 3 recruiting centers. All patients on the treatment arm will complete up to 18 cycles of Neo-MASCT treatment. Patients on the control arm will be actively monitored after randomization. Blood samples for immune response test will be taken at baseline, cycle 1day 1 and then 3 monthly on day 1 of the subsequent cycles. The planned treatment duration will be until relapse of disease, unacceptable toxicity or withdrawal of consent. The end of the trial will be 24 months after the recruitment of the last patient.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria before resection/RFA:

1. Aged = 18 years;

2. Primary HCC received RFA/Hepatectomy as the initial treatment; a solitary tumour 2.0-5.0m in diameter; or 2-3 tumours with the largest =5.0cm; all without vascular invasion, lymphatic metastasis or distant metastasis (see Appendix 1 for diagnosis criteria).

3. ECOG 0/1 (Appendix 3);

4. Child-Pugh score 5-7 (Appendix 4);

5. A life expectancy of 6 months or more;

6. Adequate haematological, liver and renal function Neutrophil count =1.5 x 109/L; platelet count> 60 x 109/L; Haemoglobin concentration=9.0 g/dL; Serum albumin= 3.0 g/dL; A total bilirubin of less than 1.5 times upper limit of normal; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 3 times upper limit of normal; Prothrombin time =3s above the control Serum creatinine concentration of 1.5 times the upper limit of the normal range or less; CCR =60ml/min

7. Written informed consent

Exclusion Criteria:

1. Pregnant women, lactating women or women planning to be pregnant in 2 years;

2. Intrahepatic metastasis, tumour thrombosis in main trunk or main branches of portal vein, tumour thrombosis in hepatic vein;

3. Systematic use of potent immunosuppressive agents within 6 months or long-term use of them such as corticosteroids, cyclosporine A, et al;

4. Concomitant HIV or HCV infection;

5. Concomitant immunodeficiency diseases or autoimmune diseases (eg. rheumatoid arthritis, Buerger's disease, multiple sclerosis and type I diabetes);

6. Concomitant malignancy or previous malignancy within 5 years before enrolment, excluding skin cancer, local prostate cancer or cervical carcinoma in situ;

7. Organ transplant recipients;

8. Patients with active auto-immune disorder, e.g. autoimmune hepatitis, systemic lupus erythematous etc.;

9. Severe dysfunction of the heart, kidney, or other organs;

10. Severe psychological dysfunction;

11. Sensitive to cytokines, any reagent or associated component in MASCT;

12. Ever participated in any clinical trial of other drugs within 3 months before enrolment;

13. Other patients that investigators think unsuitable to be enrolled.

Inclusion Criteria before immunotherapy:

1. Imaging (enhanced CT or MRI) confirmed completely tumor necrosis or tumor removed 4 weeks after RFA/Hepatectomy;

2. Obtaining adequate samples of the matched tumor and adjacent nontumor normal liver tissues;

3. Sensitive mutations can be detected by gene sequencing in tumour tissue;

4. Prediction of neoantigen peptides =10;

5. Synthesized neo antigen peptides =5.

Related Conditions & MeSH terms

• Hepatectomy
• Immunotherapy
• Primary Liver Cancer
• Radiofrequency Ablation

Intervention

Biological:
• Neo-MASCT
Patients assigned to Neo-MASCT treatment will receive 18 cycles of neo-MASCT (6 courses), with one cycle every month for the first year and one cycle every 2 months for the second year. Each cycle includes one DCs subcutaneous injection and one CTLs infusion.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (3)

Lead Sponsor	Collaborator
Sun Yat-sen University	Sixth Affiliated Hospital, Sun Yat-sen University, The First Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

References & Publications (5)

Ali MY, Grimm CF, Ritter M, Mohr L, Allgaier HP, Weth R, Bocher WO, Endrulat K, Blum HE, Geissler M. Activation of dendritic cells by local ablation of hepatocellular carcinoma. J Hepatol. 2005 Nov;43(5):817-22. Epub 2005 Jun 20. — View Citation

Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20. Review. — View Citation

Peng ZW, Zhang YJ, Chen MS, Xu L, Liang HH, Lin XJ, Guo RP, Zhang YQ, Lau WY. Radiofrequency ablation with or without transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a prospective randomized trial. J Clin Oncol. 2013 Feb 1;31(4):426-32. doi: 10.1200/JCO.2012.42.9936. Epub 2012 Dec 26. — View Citation

Shi L, Chen L, Wu C, Zhu Y, Xu B, Zheng X, Sun M, Wen W, Dai X, Yang M, Lv Q, Lu B, Jiang J. PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor. Clin Cancer Res. 2016 Mar 1;22(5):1173-1184. doi: 10.1158/1078-0432.CCR-15-1352. — View Citation

Wissniowski TT, Hänsler J, Neureiter D, Frieser M, Schaber S, Esslinger B, Voll R, Strobel D, Hahn EG, Schuppan D. Activation of tumor-specific T lymphocytes by radio-frequency ablation of the VX2 hepatoma in rabbits. Cancer Res. 2003 Oct 1;63(19):6496-500. Erratum in: Cancer Res. 2003 Nov 1;63(21):7543. Wissniowski, Thadäus Till [corrected to Wissniowski, Thaddäus Till]; Hünsler, Johannes [corrected to Hänsler, Johannes]. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival	Defined in whole days as the time from randomisation until disease recurrence or death from any cause, whichever happens first. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive and relapse free. Patients not having an event will be censored at the date last seen alive and relapse free.	2-year
Primary	Immune response rate	The demonstration of immune response is potentially related to prognosis and will be quantified in both groups because ablative therapy alone has been shown to induce anti-tumour immune responses.	2-year
Secondary	Overall survival	Defined in whole days as the time from randomisation until death from any cause. Patients who withdraw or who are lost to follow-up will be censored at the date last known to be alive. Patients remaining alive throughout the duration of the study will have their survival time censored on the date last seen alive.	2-year
Secondary	Recurrence rate	The rate of HCC recurrence in the total number of patients.	2-year
Secondary	Safety events	Safety events will be measured in terms of the occurrence, severity, type and causality of Adverse Events (AEs) during the treatment period using Common Terminology Criteria for Adverse Events (CTCAE) (version 4).	2-year