Phase II Study of Moderate-dose Hypofractionated RT Combined With Pembrolizumab for HCC With Diffuse Tumor Thrombosis
Phase II Study of Moderate-dose Hypofractionated Radiotherapy Combined With Pembrolizumab for Hepatocellular Carcinoma With Diffuse Tumor Thrombosis Involved Both Left and Right Liver
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
30 participants
May 1, 2024
INTERVENTIONAL
Conditions
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 Pembrolizumab at a dose of 200mg. Subsequently, Pembrolizumab 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 Pembrolizumab 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.
Eligibility
Inclusion Criteria12
- Confirmed clinically or histopathologically as hepatocellular carcinoma, concurrently with portal vein thrombosis or hepatic vein thrombosis;
- Age 18-90 years;
- Liver-GTV volume\<700ml or the estimated volume of Liver-GTV receiving less than 5 Gy of irradiation\<300ml but the average dose of Liver-GTV needs to be \<18Gy;
- Allowed previous treatment including TACE, RFA, surgery, chemotherapy, targeted therapy, etc., but not including ICIs such as anti-PD-1, anti-PD-L1, or anti-PD-L2 therapies;
- ECOG performance status 0-2, expected survival greater than 1 month;
- Allowing patients with distant metastases;
- Child-Pugh A5, A6, B7 and B8;
- ALT within 2.5 times the normal upper limit; AST within 2.5 times the normal upper limit; TBIL \<60umol/L.
- No significant abnormalities in the electrocardiogram, no apparent heart failure, and no contraindications for anti-PD-1 treatment;
- CRE, BUN within 2.5 times the normal upper limit;
- Hb ≥ 50g/L, ANC ≥ 0.5 × 10\^9 /L, PLT ≥ 30 × 10\^9 /L; patients with a history of gastrointestinal bleeding must be controlled for more than 2 weeks before enrollment with Hb ≥ 60g/L and a significant rising trend;
- Patients voluntarily participate in this clinical trial and sign an informed consent form.
Exclusion Criteria8
- Currently participating in other clinical trials;
- Previously received abdominal radiotherapy or liver transplantation;
- Individuals with severe chronic disease conditions affecting vital organs such as the heart, kidneys, or liver;
- Severe ascites with noticeable symptoms, anticipated to be unrelieved after treatment.
- Suspected or confirmed drug addiction, medicine abuse,or alcoholism
- Pregnant or lactating women;
- Severe mental or neurological disorders
- Presence of other life-threatening malignancy within the last 3 years before the start of the study (excluding superficial skin cancer, localized low-grade malignant tumor and in situ carcinoma).
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.
One week before or during the radiotherapy, patients receive concurrent Pembrolizumab at a dose of 200mg. Subsequently, Pembrolizumab 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 Pembrolizumab if there are no contraindications. Maintenance therapy is continued until disease progression or intolerance.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06389422