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

NCT03067493 | Unknown Phase 2 DMC

• 1 other identifier: HCC008
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Liver Cancer; Radiofrequency Ablation; Immunotherapy; Hepatectomy

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Overall survival

  2-year

• Recurrence rate

  2-year

• Safety events

  2-year

Study Arms (2)

Neo-MASCT group

EXPERIMENTAL

Patients in the treatment group will receive a total of 6 courses of Neo-MASCT treatment. The whole period of Neo-MASCT treatment for each patient will be up to 24 months.Three stratification factors are considered, i.e.tumor size (2.1-3.0cm, 3.1-5.0cm), tumor number (1, \>1) and type of surgery (RFA，hepatectomy).

Biological: Neo-MASCT

Control group

NO INTERVENTION

Patients in the control group will be actively monitored during the trial period. Patients will receive assessment every 3 months in the first 3 years.

Interventions

Neo-MASCT BIOLOGICAL

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.

Neo-MASCT group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years;
• 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).
• ECOG 0/1 (Appendix 3);
• Child-Pugh score 5-7 (Appendix 4);
• A life expectancy of 6 months or more；
• 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
• Written informed consent

You may not qualify if:

• Pregnant women, lactating women or women planning to be pregnant in 2 years;
• Intrahepatic metastasis, tumour thrombosis in main trunk or main branches of portal vein, tumour thrombosis in hepatic vein;
• Systematic use of potent immunosuppressive agents within 6 months or long-term use of them such as corticosteroids, cyclosporine A, et al;
• Concomitant HIV or HCV infection;
• Concomitant immunodeficiency diseases or autoimmune diseases (eg. rheumatoid arthritis, Buerger's disease, multiple sclerosis and type I diabetes);
• Concomitant malignancy or previous malignancy within 5 years before enrolment, excluding skin cancer, local prostate cancer or cervical carcinoma in situ;
• Organ transplant recipients;
• Patients with active auto-immune disorder, e.g. autoimmune hepatitis, systemic lupus erythematous etc.;
• Severe dysfunction of the heart, kidney, or other organs;
• Severe psychological dysfunction;
• Sensitive to cytokines, any reagent or associated component in MASCT;
• Ever participated in any clinical trial of other drugs within 3 months before enrolment;
• Other patients that investigators think unsuitable to be enrolled.
• Imaging (enhanced CT or MRI) confirmed completely tumor necrosis or tumor removed 4 weeks after RFA/Hepatectomy；
• Obtaining adequate samples of the matched tumor and adjacent nontumor normal liver tissues;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Sixth Affiliated Hospital, Sun Yat-sen University: collaborator
• The First Affiliated Hospital of Guangzhou Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 23269991 BACKGROUND

• 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. doi: 10.1016/j.jhep.2005.04.016. Epub 2005 Jun 20.

  PMID: 16087270 BACKGROUND

• 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.

  PMID: 26933175 BACKGROUND

• Wissniowski TT, Hansler 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.

  PMID: 14559842 BACKGROUND

• 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.

  PMID: 22353262 BACKGROUND

• Peng S, Chen S, Hu W, Mei J, Zeng X, Su T, Wang W, Chen Z, Xiao H, Zhou Q, Li B, Xie Y, Hu H, He M, Han Y, Tang L, Ma Y, Li X, Zhou X, Dai Z, Liu Z, Tan J, Xu L, Li S, Shen S, Li D, Lai J, Peng B, Peng Z, Kuang M. Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma. Cancer Immunol Res. 2022 Jun 3;10(6):728-744. doi: 10.1158/2326-6066.CIR-21-0931.

  PMID: 35476700 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Ming Kuang, Ph.D.

  First Affiliated Hospital, Sun Yat-Sen University

  STUDY CHAIR

Central Study Contacts

Ming Kuang, Ph.D.

CONTACT

008687755766; kuangm@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 26, 2017
• First Posted: March 1, 2017
• Study Start: July 25, 2017
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: January 26, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)