Hepatocellular CarcinomaNCT05701553
Anti-PD-1/PD-L1 Antibodies Plus S-adenosyl-methionine Treatment in Patients With Advanced-Stage Hepatocellular Carcinoma
An observational study of Hepatocellular Carcinoma, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of SAM and anti-PD-1/PDL1 antibodies for patients with advanced hepatocellular carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Anti-PD-1/PD-L1 and S-Adenosyl-Methionine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 26 Jan 2023to 31 Dec 2025
- How long will I take part?
- 2 Years
- Phase
- Observational
- 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 to 90 years
- All sexes
- Adult, Older adult
Study population: Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
Who may be able to join
- ≥18 years old, male or female
- Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Patient has given written informed consent.
- The function of important organs meets the requirements
- Expected survival ≥12 weeks
- Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.
Who cannot join
- The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included);
- The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment;
- Have clinical symptoms or disease that are not well controlled;
- Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization;
- Arterial/venous thrombosis in the first 6 months of randomization
- According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.#with family or social factors, it will affect the safety of patients.
- Liver tumor burden greater than 50% of the total liver volume, or patients who have previously undergone liver transplantation;Known for a history of central nervous system metastasis or hepatic encephalopathy;Severe allergic reactions to other monoclonal antibodies;
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Zhongshan Hospital Fudan university
Shanghai
Mincheng Yu
About this study
Official title: Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With S-adenosyl-methionine in Patients With Advanced-Stage Hepatocellular Carcinoma
This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of SAM and anti-PD-1/PDL1 antibodies for patients with advanced hepatocellular carcinoma.
Read the detailed description
This is a study of combination anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine (SAM) for adult patients (≥18) with advanced hepatocellular carcinoma.
SAM is a compound found naturally in the body and is available as a dietary supplement in the U.S. SAM is a prescription drug in China treating liver disease and advanced HCC with poor liver function under certain circumstances. Also, SAM has recently been shown to play a key role regulating cancer cell proliferation trough epigenetic pathway.
Anti-PD-1/PD-L1 antibodies (including pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab and atezolizumab etc.) are given intravenously at assigned dose. Treatment may continue until disease progression, intolerable toxicity, or consent withdrawal.
This study is aimed to evaluate the safety and efficacy of the combination of SAM and PD-1/PD-L1 monoclonal antibody in unresectable late-stage HCC patients.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Anti-PD-1/PD-L1, S-Adenosyl-Methionine
- Keywords
- Hepatocellular Carcinoma, Anti-PD-1 antibody, Anti-PD-L1 antibody, SAM
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-PD-1/PD-L1Drug
Intravenous injection at indicated dose for at least 6 months
S-Adenosyl-MethionineDrug
Also called SAM
Taken orally at indicated dose for at least 6 months
| Study group | Role | What they receive |
|---|---|---|
| Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination | Drug: Anti-PD-1/PD-L1 Intravenous injection for at least 6 months
Drug: S-adenosyl-methionine Taken orally for at least 6 months Receives: Drug: Anti-PD-1/PD-L1; Drug: S-Adenosyl-Methionine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Measured: Up to 30 days after last treatment dose
Secondary outcomes (7)
Objective response rate(ORR)
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 2 years
Progression free survival(PFS)
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 2 years
To the relief time (TOR)
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 2 years
Duration of relief(DOR)
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 2 years
Disease Control Rate (DCR)
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 2 years
6-month survival rate
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 6 months
12-month survival rate
Evaluated by researchers based on the RECIST 1.1 standard
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2023
- Study start26 Jan 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jia Fan, Principal investigator, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05701553
- Sponsor's protocol ID
- B2022-118
- Status last verified
- Jan 2023
- First submitted
- 18 Jan 2023
- Last updated
- 2 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.
PubMed 33442540Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.
PubMed 31790344Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012 Oct;92(4):1515-42. doi: 10.1152/physrev.00047.2011.
PubMed 23073625Kraeuchi K, Rudolph K, Wirz-Justice A, Feer H. Similarities in feeding behavior of chronic methamphetamine treated and withdrawn rats to VMH lesioned rats. Pharmacol Biochem Behav. 1985 Dec;23(6):917-20. doi: 10.1016/0091-3057(85)90092-9.
PubMed 4080776
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With S-adenosyl-methionine in Patients With Advanced-Stage Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT05701553
- Acronym / sponsor ID
- B2022-118
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma, Anti-PD-1 antibody, Anti-PD-L1 antibody, SAM
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Study start
- 26 Jan 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 27 Jan 2023 (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.
This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of SAM and anti-PD-1/PDL1 antibodies for patients with advanced hepatocellular carcinoma.
Detailed description
This is a study of combination anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine (SAM) for adult patients (≥18) with advanced hepatocellular carcinoma.
SAM is a compound found naturally in the body and is available as a dietary supplement in the U.S. SAM is a prescription drug in China treating liver disease and advanced HCC with poor liver function under certain circumstances. Also, SAM has recently been shown to play a key role regulating cancer cell proliferation trough epigenetic pathway.
Anti-PD-1/PD-L1 antibodies (including pembrolizumab, nivolumab, sintilimab, toripalimab, camrelizumab, tislelizumab and atezolizumab etc.) are given intravenously at assigned dose. Treatment may continue until disease progression, intolerable toxicity, or consent withdrawal.
This study is aimed to evaluate the safety and efficacy of the combination of SAM and PD-1/PD-L1 monoclonal antibody in unresectable late-stage HCC patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination | – | Drug: Anti-PD-1/PD-L1, Drug: S-Adenosyl-MethionineDrug: Anti-PD-1/PD-L1 Intravenous injection for at least 6 months Drug: S-adenosyl-methionine Taken orally for at least 6 months |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
Key inclusion criteria (7 listed)
- ≥18 years old, male or female
- Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
- Patient has given written informed consent.
- The function of important organs meets the requirements
Key exclusion criteria (7 listed)
- The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included);
- The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount > 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment;
- Have clinical symptoms or disease that are not well controlled;
- Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization;
- Arterial/venous thrombosis in the first 6 months of randomization
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 |
|---|---|---|
| Anti-PD-1/PD-L1Intravenous injection at indicated dose for at least 6 months | Drug | Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination |
| S-Adenosyl-MethionineAlso: SAMTaken orally at indicated dose for at least 6 months | Drug | Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination |
Primary outcome
Incidence of adverse events
Time frame: Up to 30 days after last treatment dose
Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
7 secondary outcomes
Objective response rate(ORR)
Time frame: 2 years
Progression free survival(PFS)
Time frame: 2 years
To the relief time (TOR)
Time frame: 2 years
Duration of relief(DOR)
Time frame: 2 years
Disease Control Rate (DCR)
Time frame: 2 years
6-month survival rate
Time frame: 6 months
12-month survival rate
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2023.
- Background: PubMed 33442540Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.
- Background: PubMed 31790344Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.
- Background: PubMed 23073625Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiol Rev. 2012 Oct;92(4):1515-42. doi: 10.1152/physrev.00047.2011.
- Background: PubMed 4080776Kraeuchi K, Rudolph K, Wirz-Justice A, Feer H. Similarities in feeding behavior of chronic methamphetamine treated and withdrawn rats to VMH lesioned rats. Pharmacol Biochem Behav. 1985 Dec;23(6):917-20. doi: 10.1016/0091-3057(85)90092-9.
- 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.
Jia Fan principal investigator
Fudan University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Shanghai Zhongshan Hospital 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 7 inclusion and 7 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 2 Feb 2023. 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.
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 Mincheng Yu (2164041990, yumincheng94@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Up to 30 days after last treatment dose). 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 NCT05701553, which also lists 4 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 2 Feb 2023.