Anti-PD-1/PD-L1 Antibodies Plus S-adenosyl-methionine Treatment in Patients With Advanced-Stage Hepatocellular Carcinoma

NCT05701553 | Unknown

• 1 other identifier: B2022-118
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatocellular Carcinoma; Anti-PD-1 antibody; Anti-PD-L1 antibody; SAM

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 30 days after last treatment dose

Secondary Outcomes (7)

• Objective response rate(ORR)

  2 years

• Progression free survival(PFS)

  2 years

• To the relief time (TOR)

  2 years

• Duration of relief(DOR)

  2 years

• Disease Control Rate (DCR)

  2 years

Study Arms (1)

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

Drug: Anti-PD-1/PD-L1; Drug: S-Adenosyl-Methionine

Interventions

Anti-PD-1/PD-L1 DRUG

Intravenous injection at indicated dose for at least 6 months

Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination

S-Adenosyl-Methionine DRUG

Taken orally at indicated dose for at least 6 months

Also known as: SAM

Anti-PD-1/PD-L1 antibodies and S-adenosyl-methionine combination

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• ≥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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital Fudan university

Shanghai, China

RECRUITING

Related Publications (4)

• 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.

  PMID: 33442540 BACKGROUND

• Finn 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.

  PMID: 31790344 BACKGROUND

• Lu 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.

  PMID: 23073625 BACKGROUND

• Kraeuchi 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.

  PMID: 4080776 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood specimen and tissue samples will be collected performing related experiments including metabolomics analysis, lipidomics analysis and flow cytometry etc.

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

S-Adenosylmethionine

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

Intervention Hierarchy (Ancestors)

Methionine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Amino Acids; Amino Acids, Peptides, and Proteins; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Jia Fan

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mincheng Yu

CONTACT

2164041990; yumincheng94@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 27, 2023
• Study Start: January 26, 2023
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: February 2, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)