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

Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05701553
• Other study ID #: B2022-118
• Status: Recruiting
• Start date: January 26, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2023
• Source: Shanghai Zhongshan Hospital
• Contact: Mincheng Yu
• Phone: 2164041990
• Email: yumincheng94[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Anti-PD-1/PD-L1
Intravenous injection at indicated dose for at least 6 months
• S-Adenosyl-Methionine
Taken orally at indicated dose for at least 6 months

Locations

Country	Name	City	State
China	Zhongshan Hospital Fudan university	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate(ORR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Secondary	Progression free survival(PFS)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Secondary	To the relief time (TOR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Secondary	Duration of relief(DOR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Secondary	Disease Control Rate (DCR)	Evaluated by researchers based on the RECIST 1.1 standard	2 years
Secondary	6-month survival rate	Evaluated by researchers based on the RECIST 1.1 standard	6 months
Secondary	12-month survival rate	Evaluated by researchers based on the RECIST 1.1 standard	12 months