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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma; Radiotherapy; Pembrolizumab; Tumor Thrombosis
• Intervention / Treatment: Radiation: Moderate-dose Hypofractionated Intensity-modulated Radiotherapy; Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciecnces and Peking Union Medical College
      • Contact: Bo Chen, MD; Phone Number: 0086-13240000876; Email: chenboo@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiotherapy and 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.

Radiation: Moderate-dose Hypofractionated Intensity-modulated Radiotherapy; 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.; Drug: Pembrolizumab; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Overall Survival	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	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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	Assessment in 1 to 3 months after radiotherapy
Progression-free Survival	Progression-free Survival (PFS) is defined as the time from the end of RT until tumor progression or death from any cause.	24 months
Toxicity	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).	up to 24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Radiotherapy; Pembrolizumab; Tumor Thrombosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Embolism and Thrombosis; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Thrombosis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: NCC4620

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes