Primary Liver CancerPhase 2RAMECNCT03067493
RFA or Surgical Resection Combined With Neo-MASCT for Primary HCC: a Phase II Trial
A Phase 2 study testing Neo-MASCT in people with Primary Liver Cancer and Radiofrequency Ablation, run by Sun Yat-sen University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Liver Cancer, Radiofrequency Ablation, Immunotherapy
- What is being tested?
- Neo-MASCT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 98 participants
- Where
- 1 siteChina
- Study dates
- 25 Jul 2017to 31 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- Written informed consent
- 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;
- Sensitive mutations can be detected by gene sequencing in tumour tissue;
- Prediction of neoantigen peptides ≥10;
- Synthesized neo antigen peptides ≥5.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080
Ming Kuang, Ph.D., 008687755766 ext. 8576, kuangm@mail.sysu.edu.cn
About this study
Official title: Radiofrequency Ablation or Surgical Resection Combined With Neo-MASCT for Primary Hepatocellular Carcinoma: a Randomised, Multicentre Phase II Trial
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.
Read the detailed 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.
- Being tested
- Neo-MASCT
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Neo-MASCTBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2-year
Secondary outcomes (3)
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.
Measured: 2-year
Recurrence rate
The rate of HCC recurrence in the total number of patients.
Measured: 2-year
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).
Measured: 2-year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2017
- Study start25 Jul 2017
- Primary completion31 Mar 2023 (estimated)
- Study completion31 Mar 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Primary Liver CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 98 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Sixth Affiliated Hospital, Sun Yat-sen University, The First Affiliated Hospital of Guangzhou Medical University
- Responsible party
- Principal investigator, Ming Kuang, Sun Yat-sen University
- Investigators
- Ming Kuang, Ph.D., Study chair, First Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03067493
- Sponsor's protocol ID
- HCC008
- Acronym
- RAMEC
- Status last verified
- Jan 2022
- First submitted
- 26 Feb 2017
- Last updated
- 26 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23269991Ali 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.
PubMed 16087270Shi 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.
PubMed 26933175Wissniowski 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.
PubMed 14559842Forner 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.
PubMed 22353262Peng 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.
PubMed 35476700
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiofrequency Ablation or Surgical Resection Combined With Neo-MASCT for Primary Hepatocellular Carcinoma: a Randomised, Multicentre Phase II Trial
- ClinicalTrials.gov ID
- NCT03067493
- Acronym / sponsor ID
- RAMEC / HCC008
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 98 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Sixth Affiliated Hospital, Sun Yat-sen University, The First Affiliated Hospital of Guangzhou Medical University
- Study start
- 25 Jul 2017 (actual)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 31 Mar 2023 (estimated)
- First posted
- 1 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neo-MASCT group | Experimental | Biological: Neo-MASCTPatients 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). |
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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;
Key exclusion criteria (13 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neo-MASCTPatients 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. | Biological | Neo-MASCT group |
Primary outcome
Disease free survival
Time frame: 2-year
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.
Immune response rate
Time frame: 2-year
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.
3 secondary outcomes
Overall survival
Time frame: 2-year
Recurrence rate
Time frame: 2-year
Safety events
Time frame: 2-year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2022.
- Background: PubMed 23269991Peng 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.
- Background: PubMed 16087270Ali 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.
- Background: PubMed 26933175Shi 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.
- Background: PubMed 14559842Wissniowski 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.
- Background: PubMed 22353262Forner 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.
- Derived from this study: PubMed 35476700Peng 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ming Kuang, Ph.D. study chair
First Affiliated Hospital, Sun Yat-Sen University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neo-MASCT in people with Primary Liver Cancer and Radiofrequency Ablation, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ming Kuang, Ph.D. (008687755766 ext. 8576, kuangm@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease free survival (time frame: 2-year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03067493, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2022.