Clinical trial NCT05701553: Anti-PD-1/PD-L1 Antibodies Plus S-adenosyl-methionine Treatment in Patients With Advanced-Stage Hepatocellular Carcinoma
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular Carcinoma
Anti-PD-1 antibody
Anti-PD-L1 antibody
SAM
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2023-01-27
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. ≥18 years old, male or female
2. 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
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
4. Patient has given written informed consent.
5. The function of important organs meets the requirements
6. Expected survival ≥12 weeks
7. 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.

Exclusion Criteria:

1. 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);
2. 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;
3. Have clinical symptoms or disease that are not well controlled;
4. Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization;
5. Arterial/venous thrombosis in the first 6 months of randomization
6. 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.
7. 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;

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 30 days after last treatment dose
Secondary outcomes:
measure: Objective response rate(ORR)
timeFrame: 2 years
measure: Progression free survival(PFS)
timeFrame: 2 years
measure: To the relief time (TOR)
timeFrame: 2 years
measure: Duration of relief(DOR)
timeFrame: 2 years
measure: Disease Control Rate (DCR)
timeFrame: 2 years
measure: 6-month survival rate
timeFrame: 6 months
measure: 12-month survival rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan university
Study officials:
affiliation: Fudan University
name: Jia Fan
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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