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

Sponsor

Shanghai Zhongshan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05701553

Collaborator

(none)

Enrollment

Location

35.2

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Anti-PD-1/PD-L1 Drug: S-Adenosyl-Methionine

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

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Actual Study Start Date :

Jan 26, 2023

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
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 Intravenous injection at indicated dose for at least 6 months Drug: S-Adenosyl-Methionine Taken orally at indicated dose for at least 6 months Other Names: SAM

Arm

Intervention/Treatment

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

Intravenous injection at indicated dose for at least 6 months

Drug: S-Adenosyl-Methionine

Taken orally at indicated dose for at least 6 months

Other Names:

SAM

Outcome Measures

Primary Outcome Measures

Incidence of adverse events [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.

Secondary Outcome Measures

Objective response rate(ORR) [2 years]
Evaluated by researchers based on the RECIST 1.1 standard
Progression free survival(PFS) [2 years]
Evaluated by researchers based on the RECIST 1.1 standard
To the relief time (TOR) [2 years]
Evaluated by researchers based on the RECIST 1.1 standard
Duration of relief(DOR) [2 years]
Evaluated by researchers based on the RECIST 1.1 standard
Disease Control Rate (DCR) [2 years]
Evaluated by researchers based on the RECIST 1.1 standard
6-month survival rate [6 months]
Evaluated by researchers based on the RECIST 1.1 standard
12-month survival rate [12 months]
Evaluated by researchers based on the RECIST 1.1 standard

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

≥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.

Exclusion Criteria:

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;