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

NCT06389422 | Recruiting Phase 2 FDA Drug

• 1 other identifier: NCC4620
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatocellular Carcinoma; Radiotherapy; Pembrolizumab; Tumor Thrombosis

Keywords

Hepatocellular Carcinoma; Radiotherapy; Pembrolizumab; Tumor Thrombosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Objective Response Rate

  Assessment in 1 to 3 months after radiotherapy

• Progression-free Survival

  24 months

• Toxicity

  up to 24 months

Study Arms (1)

Radiotherapy and Pembrolizumab

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

Moderate-dose Hypofractionated Intensity-modulated Radiotherapy RADIATION

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.

Radiotherapy and Pembrolizumab

Pembrolizumab DRUG

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.

Radiotherapy and Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

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

Study Sites (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciecnces and Peking Union Medical College

Beijing, Beijing Municipality, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: April 29, 2024
• Study Start: May 1, 2024
• Primary Completion: April 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: April 29, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)