Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular Carcinoma, Anti-PD-1 antibody, Anti-PD-L1 antibody, SAM
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.
Interventions
DRUGAnti-PD-1/PD-L1
Intravenous injection at indicated dose for at least 6 months
DRUGS-Adenosyl-Methionine
Taken orally at indicated dose for at least 6 months
Sponsors
Shanghai Zhongshan Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Objective response rate(ORR) | 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 |
| Disease Control Rate (DCR) | 2 years | Evaluated by researchers based on the RECIST 1.1 standard |
Countries
China
Contacts
Primary ContactMincheng Yu
Outcome results
None listed