Hepatocellular Carcinoma, Radiotherapy, Tislelizumab, Tumor Thrombosis
Conditions
Keywords
Hepatocellular Carcinoma, Radiotherapy, Tislelizumab, Tumor Thrombosis
Brief summary
This is a single-center, single-arm, open-label study that includes patients meeting the inclusion criteria (liver-GTV volume \< 700ml or estimated liver-GTV V5 \< 300ml) with hepatocellular carcinoma with diffuse tumor thrombosis involving both left and right lobes. All lesions receive moderate-dose hypofractionated intensity-modulated radiotherapy, with a gross tumor dose of 25Gy/5f, and a maximum dose of 35Gy/5f at the tumor center. One week before or during the radiotherapy, patients receive concurrent Tislelizumab at a dose of 200mg. Subsequently, Tislelizumab is administered intravenously every 3 weeks. Follow-up examinations are conducted 1-3 months post-radiotherapy. Lenvatinib 4mg may be used for maintenance therapy with Tislelizumab if there are no contraindications. Maintenance therapy is continued until disease progression or intolerance. The primary endpoint is median overall survival (mOS), and secondary endpoints include objective response rate (ORR), progression-free survival (PFS), and toxicity.
Interventions
All lesions receive moderate-dose hypofractionated intensity-modulated radiotherapy, with a gross tumor dose of 25Gy/5f, and a maximum dose of 35Gy/5f at the tumor center.
DRUGTislelizumab
One week before or during the radiotherapy, patients receive concurrent Tislelizumab at a dose of 200mg. Subsequently, Tislelizumab is administered intravenously every 3 weeks. Follow-up examinations are conducted 1-3 months post-radiotherapy. Lenvatinib 4mg may be used for maintenance therapy with Tislelizumab, which may be escalated up to a maximum of 12 mg per day, until disease progression or intolerance or death.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical or histological diagnosis of HCC with bilateral PVTT; 2. Estimated Liver-GTV volume \< 700ml or the estimated volume of liver minus GTV volume receiving less than 5 Gy of irradiation \< 300ml; 3. Age 18-90 years; 4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; 5. Child-Pugh A5, A6, B7 and B8; 6. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times upper limit of normal (ULN); or ALT ≤ 1.5 times ULN and AST ≤ 6 times ULN; TBIL \< 60umol/L. 7. Creatinine (CRE) and blood urea nitrogen (BUN) \< 2.5 ULN; 8. Hb ≥ 50g/L, ANC ≥ 0.5 × 109/L, PLT ≥ 30 × 109 /L; patients with a history of gastrointestinal bleeding must be controlled for more than 2 weeks before enrollment with Hb ≥ 60g/L; 10\. Voluntary to participate and sign informed consent.
Exclusion criteria
1. Participating in other clinical trials currently; 2. The history of abdominal irradiation; 3. The history of liver transplantation; 4. Known allergy to tislelizumab or lenvatinib; 5. Pregnant, breast feeding, or unwilling to use adequate contraception; 6. Serious myocardial disease or renal failure; 7. Other serious diseases, such as alcohol and drug abuse or mental illness; 8. Presence of other life-threatening malignancy within the last 3 years before enrollment (excluding superficial skin cancer, localized low-grade malignant tumor and carcinoma in situ).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | 24 months | Median Overall Survival (mOS) is defined as the median of Overall Survival (OS). OS is defined as the time from the end of radiotherapy to death from any cause |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Assessment in 1 to 3 months after radiotherapy | Treatment response was defined as the best response in 3 months after radiotherapy. ORR is defined as the percentage of patients who met the complete response (CR) or partial response (PR) criteria as defined by the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and RECIST 1.1 |
| Progression-free Survival | 24 months | Progression-free Survival (PFS) is defined as the time from the end of RT until tumor progression or death from any cause. |
| Toxicity | up to 24 months | Toxicity is assessed and graded according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). |
Countries
China
Outcome results
None listed