Phase 2 Study of SBRT Plus Tislelizumab and Regorafenib in Unresectable or Oligometastatic HCC

Study Overview
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Brief Summary
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The goal of this phase 2 prospective clinical trial is to learn about the efficacy and safety of stereotactic body radiation therapy (SBRT) plus immunotherapy and targeted therapy in patients with unresectable or oligometastatic hepatocellular carcinoma (HCC). The main question to answer is: Whether combing SBRT with immunotherapy and targeted therapy could prolong PFS. Participants will receive SBRT to all visible lesions and concurrent systemic immunotherapy and targeted therapy.

Official Title
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Phase 2 Study of Stereotactic Body Radiation Therapy Plus Tislelizumab and Regorafenib in Unresectable or Oligometastatic Hepatocellular Carcinoma

Conditions
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Unresectable Hepatocellular Carcinoma, Oligometastatic Disease

Intervention / Treatment
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* Combination Product: SBRT plus tislelizumab and regorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years Eastern Cooperative Oncology Group performance status of 0-1 clinical or pathological diagnosis of HCC with unresectable locally advanced or oligometastatic HCC (metastatic lesions ≤ 5, metastatic organs ≤ 3, may involve extrahepatic lymph nodes or distant organs apart from brain) at least one measurable lesion according to mRECIST criteria all lesions could be included in radiation target volume Child-Pugh A or B (7 scores) liver function patients are allowed to receive systemic therapy previously other than tislelizumab plus regorafenib adequate hematological and renal function life expectancy ≥ 3 months； willing to participate in the study and give written informed consent Exclusion Criteria: a history of liver transplantation with severe cirrhosis complications, including a history of esophagogastric variceal bleeding, hepatic encephalopathy, and massive ascites with active autoimmune diseases or a history of autoimmune disease with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) allergic to the ingredient of tislelizumab or regorafenib with recurrent lesions treated with radiotherapy previously prescribed radiation does could not be delivered due to dose limits to organs at risk (OAR) intolerable to radiation or systemic treatment because of cardiac insufficiency, uncontrolled high blood pressure a history of other malignancies, except cured basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SBRT plus Tislelizumab and Regorafenib<br>Participants will receive SBRT (8 Gy × 3-5 fractions) to all visible lesions. Systemic treatment (tislelizumab and regorafenib) will start concurrently and last for 2 years, or until disease progression, intolerable side-effects or death. Tislelizumab will be delivered every 21 days at a dose of 200mg, and regorafenib will be given at a dose of 120mg for the first 21 days of a 28-day cycle. Appropriate dose adjustments of regorafenib will be made if side-effects are intolerable, while the dose of tislelizumab should not be adjusted, but could be paused. | Combination Product: SBRT plus tislelizumab and regorafenib<br>* Participants will receive SBRT plus tislelizumab and regorafenib concurrently<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | From the date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall survival | From the date of treatment beginning until the date of death from any cause, assessed up to 48 months | 
| Recurrence pattern | Number of participants with recurrence, which will be classified according to site of recurrence (specific organs), time interval between treatment beginning and recurrence, the relationship with the area of irradiation (in-field/out field), and whether new lesion(s) according to mRECIST criteria | From the date of treatment beginning until the date of last follow-up, assessed up to 48 months |