Phase II Study of Moderate-dose Hypofractionated RT Combined With Pembrolizumab for HCC With Diffuse Tumor Thrombosis

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma; Radiotherapy; Pembrolizumab; Tumor Thrombosis
• Interventions: Radiation: Moderate-dose Hypofractionated Intensity-modulated Radiotherapy; Drug: Pembrolizumab

• Registration Number: NCT06389422
• Lead Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

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 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-24
• Study First Submitted QC: 2024-04-24
• Last Update Submitted: 2024-04-24
• Study First Posted: 2024-04-29
• Last Update Posted: 2024-04-29
• Study Start: 2024-05-01
• Primary Completion: 2026-04-30
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Confirmed clinically or histopathologically as hepatocellular carcinoma, concurrently with portal vein thrombosis or hepatic vein thrombosis;
2. Age 18-90 years;
3. 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;
4. 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;
5. ECOG performance status 0-2, expected survival greater than 1 month;
6. Allowing patients with distant metastases;
7. Child-Pugh A5, A6, B7 and B8;
8. ALT within 2.5 times the normal upper limit; AST within 2.5 times the normal upper limit; TBIL <60umol/L.
9. No significant abnormalities in the electrocardiogram, no apparent heart failure, and no contraindications for anti-PD-1 treatment;
10. CRE, BUN within 2.5 times the normal upper limit;
11. 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;
12. Patients voluntarily participate in this clinical trial and sign an informed consent form.

Exclusion Criteria

1. Currently participating in other clinical trials;
2. Previously received abdominal radiotherapy or liver transplantation;
3. Individuals with severe chronic disease conditions affecting vital organs such as the heart, kidneys, or liver;
4. Severe ascites with noticeable symptoms, anticipated to be unrelieved after treatment.
5. Suspected or confirmed drug addiction, medicine abuse,or alcoholism
6. Pregnant or lactating women;
7. Severe mental or neurological disorders
8. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiotherapy and Pembrolizumab	Moderate-dose Hypofractionated Intensity-modulated Radiotherapy	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 concurrent with Pembrolizumab, followed Pembrolizumab±lenvatinib for maintenance.
Radiotherapy and Pembrolizumab	Pembrolizumab	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 concurrent with Pembrolizumab, followed Pembrolizumab±lenvatinib for maintenance.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).; Toxicity is assessed and graded according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0).; Toxicity is assessed and graded according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0).; Toxicity is assessed and graded according to the Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0).

Trial Locations

Locations (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciecnces and Peking Union Medical College; 🇨🇳 Beijing, Beijing, China