Ablation Combined With PD-1 in HCC: Phase II Study

NCT04652440 | Unknown Phase 1

• 1 other identifier: B2020-197-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, single arm, single center study designed to evaluate the safety and tolerability of radiofrequency or microwave ablation combined with PD-1 monoclonal antibody in patients with hepatocellular carcinoma(HCC), with the secondary study objective to preliminarily evaluate the efficacy of radiofrequency or microwave ablation combined with PD-1 monoclonal antibody in patients with HCC and the exploratory study objective to evaluate the effect of ablation combined with PD-1 monoclonal antibody on immune function and hepatitis virus infection status in patients with HCC. This study will be divided into two stages, and the first stage is to enroll 6 patients for dose-limited toxicity (DLT) observation. If DLT appeared in \< 2 patients, the second stage was entered and the other 24 patients were further enrolled.

Conditions

Hepatocellular Carcinoma

Keywords

Radiofrequency ablation; PD-1 Inhibitor; Hepatocellular Carcinoma; Microwave ablation

Outcome Measures

Primary Outcomes (2)

• Measure Safety

  Treatment-related adverse events (TRAEs) and serious adverse events (SAEs) occurring from the start of PD-1 monoclonal antibody therapy to 90 days after treatment were observed and judged according to CTCAE 5.0 criteria.

  from the start of PD-1 monoclonal antibody therapy to 90 days after treatment

• Measure Tolerability

  Measured as the rate of patients able to complete treatment as planned in the study.

  from the start of PD-1 monoclonal antibody therapy to 90 days after treatment

Secondary Outcomes (5)

• Complete Response (CR1)

  Two years

• Treatment Failure Rate (TFR)

  Two years

• Local Recurrence Rate (LRR) and Distant Metastasis Rate (DMR)

  Two years

• 1- and 2-year disease-free survival (DFS) and overall survival (OS) rates

  Two years

• Median Disease-free survival (mDFS)

  Two years

Study Arms (1)

Radiofrequency or microwave ablation combined with PD-1 monoclonal antibody

EXPERIMENTAL

Patients who meet the inclusion criteria will receive 1 cycle of PD-1 antibody on the day before ablation, then 3 cycles of PD-1 antibody after primary radiofrequency or microwave ablation, on a schedule of per 3 weeks, then be followed until disease relapse or death.

Drug: PD-1 monoclonal antibody; Procedure: Radiofequencey or microwave ablation

Interventions

PD-1 monoclonal antibody DRUG

The enrolled patients received intravenous injections of PD-1 monoclonal antibody (Tislelizumab 200mg) on the 1 day before radiofrequency or microwave ablation treatment, and 21(±7) days, 42(+7) and 63(+7) after ablation.

Also known as: Tislelizumab

Radiofrequency or microwave ablation combined with PD-1 monoclonal antibody

Radiofequencey or microwave ablation PROCEDURE

The enrolled patients received primary radiofrequency or microwave ablation on the day after the first dose of PD-1 antibody treatment.

Also known as: ablation

Radiofrequency or microwave ablation combined with PD-1 monoclonal antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who voluntarily participate in the study and sign the informed consent form
• \~ 75 years old, both men and women
• Clinical diagnosis of hepatocellular carcinoma, conforming to the indications of radiofrequency or microwave ablation
• Child-Pugh score ≤6 (Child-Pugh score A)
• Barcelona Clinic Liver Cancer (BCLC) Stage A or B
• Number of tumors ≤ 2; 2 cm\<maximum diameter≤ 5 cm
• No distant metastasis or lymph node metastasis (defined as lymph node maximum transverse diameter ≥ 15 mm)
• ECOG score 0 or 1
• No history of drug allergy;
• The function of vital organs meets the following requirements (no blood component, cell growth factor and other corrective treatment drugs are allowed to be used 14 days before enrollment) 1）Absolute neutrophil count≥1.5×109/L; 2）Platelets≥80×109/L; 3）Hemoglobin≥90 g/L; 4）Serum albumin≥30 g/L; 5）Thyroid stimulating hormone (TSH) ≤1×ULN (if abnormal, FT3 and FT4 should also be investigated, and patients whose FT3 and FT4 levels are normal can be enrolled); 6) Bilirubin≤1.5×ULN (within 7 days prior to the first dose); 7) ALT and AST≤3×ULN (within 7 days prior to the first dose); 8) No prolongation of PT by more than 3 seconds above the ULN; 9)Serum creatinine≤1.5×ULN;
• Female patients who are not surgically sterilized or of reproductive age need to use contraceptive measures (such as intrauterine device, contraceptives or condoms) during the study treatment period and within 3 months after the end of the study treatment period; female patients of childbearing potential who are not surgically sterilized must have a negative serum or urine HCG test within 72 hours before enrollment; and must be non-lactating; male patients with partners of childbearing potential should take an effective method of contraception during the trial and within 3 months after treatment.

You may not qualify if:

• Patients unsuitable for percutaneous radiofrequency or microwave ablation for any reason
• 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, hypophysitis, vasculitis, nephritis, hyperthyroidism; vitiligo; patients with complete remission of asthma in childhood but requiring no intervention after adulthood can be included; patients with asthma requiring medical intervention with bronchodilators can not be included)
• Patients who need to use immunosuppressive agents or require systemic hormone therapy to achieve the purpose of immunosuppression (dose \> 10 mg/day prednisone or other effective hormones) and are still using them within 2 weeks before enrollment
• Prior systemic anticancer therapy
• Received or intended to receive other anticancer therapy (vascular intervention, etc.) other than surgical resection or ablative therapy
• Known history of central nervous system metastasis or hepatic encephalopathy
• Tumor necrosis cannot be confirmed by reexamination of imaging after local ablation
• Clinically symptomatic ascites requiring puncture and drainage or those who have received ascites drainage in the past 3 months, except those with only a small amount of ascites shown by imaging but not accompanied by clinical symptoms
• Hypertension not well controlled by antihypertensive medication (systolic blood pressure≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg)
• Uncontrolled cardiac clinical symptoms or diseases, such as: (1) heart failure above NYHA2; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention; (5)QTc \> 450 ms (male); QTc \> 470 ms (female)
• Abnormal coagulation function (INR \> 2.0, PT \> 16s), bleeding tendency or receiving thrombolytic or anticoagulant therapy. Prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed
• Patients with clinically significant bleeding symptoms or bleeding tendency within 3 months before randomization, such as hemoptysis more than 2.5ml per day, gastrointestinal bleeding, esophageal and gastric varices at risk of bleeding, hemorrhagic gastric ulcer, vasculitis, etc. If the stool occult blood is positive at baseline, reexamination must be performed. if it is still positive after reexamination, gastroscopy is required. If gastroscopy suggests severe esophageal and gastric varices, patients can't be enrolled (except for those who receive gastroscopy to rule out such conditions within 3 months before enrollment)
• Arterial/venous thrombotic events occurred within 6 months before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism
• Known hereditary or acquired bleeding and thrombophilia (such as hemophilia, coagulation dysfunction, thrombocytopenia, etc.)
• Urine routine test showed urine protein≥+ + and 24-hour urine protein \> 1.0 g is confirmed

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

spartalizumab; tislelizumab

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

Central Study Contacts

Min-Shan Chen, Ph.D.

CONTACT

+86-20-87343115; chenmsh@sysucc.org.cn

Li Xu

CONTACT

xuli@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Evaluate the safety and tolerability of radiofrequency ablation combined with PD-1 monoclonal antibody in the treatment of patients with hepatocellular carcinoma.

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: December 3, 2020
• Study Start: December 15, 2020
• Primary Completion: December 31, 2023
• Study Completion: June 30, 2024
• Last Updated: April 19, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: 1 year after the study complete.

Locations

CN (1)