Safety and Efficacy of TareSphere in Patients With Unresectable Hepatocellular Carcinoma

Study on the Safety and Effectiveness of NRT6003 Injection in Patients With Unresectable Hepatocellular Carcinoma (HCC)

The goal of this clinical trial is to evaluate the safety and efficacy of NRT6003 Injection in patients with unresectable HCC.

Study Overview

• Status: Completed
• Conditions: Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: NRT6003 Injection

Detailed Description

The efficacy and safety of TareSphere in patients with unresectable HCC remains unknown. This trial is a prospective, multicenter, open-label, single-arm phase I trial designed to evaluate the safety and efficacy of NRT6003 injection.

The primary objective is to evaluate the safety of NRT6003 Injection. While the secondary objectives include the assessments of the antitumoral efficacy, the improvement of patients´ quality of life, and the distribution characteristics of Yttrium-90 in body.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Zhongshan Hospital, Fudan University
  • Anhui
    • Hefei, Anhui, China
      • Anhui Provincial Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Jinan University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Provincial People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital, Southeast University
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital, Sichuan University
    • Luzhou, Sichuan, China
      • The affiliated hospital of Southwest Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Aged 18 to 80 and signed informed consent;
2. Diagnosed as hepatocellular carcinoma clinically, by imaging and/or pathology based on the guideline of the National Health Commission of the People's Republic of China (2022);
3. Evaluated by the investigator as not suitable for surgical resection/ablation, or there are other reasons unsuitable for surgical resection/ablation, or the participant refuses surgical resection/ablation;
4. At least one well defined tumor (mRECIST), assessed by enhanced MRI or CT images;
5. Child-Pugh score ≤ 7;
6. Eastern Cooperative Oncology Group performance status ≤ 1;
7. Tumor burden ≤ 50 percent of the total liver volume;
8. Adequate organ function: (1) Blood routine [no blood transfusion or granulocyte colony-stimulating factor (G-CSF) treatment within 14 days]: absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; platelet (PLT) ≥ 80 × 10^9/L; hemoglobin (HGB) ≥ 90 g/L; (2) Liver function: total bilirubin (TBIL) ≤ 2 times upper limit of normal (ULN); alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5. 0×ULN; Albumin > 30 g/L; (3) Renal function: Creatinine (Cr) ≤ 1.5×ULN; creatinine clearance rate (CCr)≥ 50 mL/min (calculated according to Cockcroft-Gault formula); (4) Coagulation function: international normalized ratio (INR), prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN [If any participant takes warfarin or heparin for anticoagulation therapy, the investigator should evaluate whether the participant meet the requirements of the protocol]; (5) Cardiovascular function: left ventricular ejection fraction (LVEF) ≥ 50 percent assessed by ultrasonic cardiogram;
9. Women and men of childbearing age must agree to take strict and effective contraceptive measures during the study period and within 6 months after the end of the trial. Men are forbidden to donate sperm. The pregnancy test results of female participants of childbearing age during the screening period and within 24 hours before administration must be negative.

Exclusion Criteria:

1. With the extrahepatic metastasis or concurrent malignant tumors other than liver cancer;
2. With the hepatic tumor thrombus (excluding the thrombus limited to liver segments or lobes);
3. With hepatic artery malformation and unable to intubate hepatic artery;
4. Allergy to contrast agents or anesthetics;
5. Severe pulmonary dysfunction (forced expiratory volume in one second, FEV1/FVC < 50 percent or forced expiratory volume in one second (FEV1) < 50 percent of predicted value, or maximum voluntary ventilation (MVV) < 50 L/min);
6. With the clinical manifestations of decompensated liver cirrhosis (moderate or severe ascites, upper gastrointestinal bleeding, hepatic encephalopathy, etc.);
7. With diseases have not been controlled despite aggressive treatment, and which may affect the safety or the efficacy of the investigational drug in the judgement of investigators;
8. Active or severely infected participants requiring systemic therapy;
9. With positive results of HIV antibody test;
10. Estimated survival period < 3 months;
11. Have received radiotherapy or transcatheter arterial chemoembolization (participants who have received transcatheter arterial non-iodized oil chemoembolization are judged by investigators);
12. Technetium (99mTc)-macroaggregated albumin (MAA) hepatic arterial perfusion imaging estimates that the NRT6003 injection cannot cover all lesions within the liver (excluding lesions previously treated by the investigator as non-active or non-progressive);
13. Hepatic artery angiography and 99mTc-MAA hepatic artery perfusion imaging demonstrate gastrointestinal shunts, which may not be remedied through vascular intervention techniques;
14. 99mTc-MAA arterial perfusion imaging shows that the single lung radiation absorbed dose > 30 Gy;
15. Received antitumor therapy or participated in other interventional clinical trials within 30 days prior to dosing;
16. Pregnant or lactating women;
17. Have persistent, unrelieved toxicity reaction of CTCAE≥2 grade caused by previous antitumor treatment (excluding alopecia) judged by investigators;
18. Any other reason that the investigator deems the participant unsuitable for participating in this trial.

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: NRT6003 Injection; Patients will be administered a single dose of NRT6003 Injection, and then they will be assessed by SPECT-CT imaging within 24 hours for its distribution in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected. Nine Patients will be tested for the radioactivity of Yttrium-90 in blood, urine, and feces (if available).

Drug: NRT6003 Injection; Selective internal radiation therapy (SIRT) with TareSphere; Other Names: Yttrium-90 carbon microspheres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events/ Severe adverse events	Occurrence of adverse events/severe adverse events	Up to 12 months
Localized Objective response rates (ORR)	Liver target lesions, evaluated based on the mRECIST criteria	Up to 6 months (initial tumor assessment after administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yttrium-90 distribution	Assessed by SPECT-CT imaging in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.	Within 24 hours
Hepatic time to progression (hTTP)	Time to progression of liver target lesions, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Duration of response (DOR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Disease control rate (DCR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Time to progression (TTP)	Time with tumor progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Progression Free Survival (PFS)	Duration from the administration to the first evidence of progression or death from any cause, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Concentration of Alpha fetoprotein (AFP)	The variation of AFP levels	Up to 12 months
Quality of life (QoL)	The variation of QoL with the EORTC (European organization for Research and Treatment of Cancer) QLG (Quality of Life Group) Core Questionnaire (EORTC QLQ-C30)	Up to 12 months
Resection rate of liver target lesions	Resection rate of liver target lesions	Within 6 months after administration
Radioactivity of Yttrium-90 for 9 participants, assessed by liquid scintillation counter	Detect the radioactivity of Yttrium-90 in blood, urine, and feces (if available) in liquid scintillation counter	Within 168 hours

Collaborators and Investigators

• Sponsor: Chengdu New Radiomedicine Technology Co. LTD.
• Investigators: Principal Investigator: Gaojun Teng, MD, Zhongda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 8, 2023
• Primary Completion (Actual): June 10, 2025
• Study Completion (Actual): June 10, 2025

Study Registration Dates

• First Submitted: February 26, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Yttrium-90; Selective internal radiation therapy; Transarterial Radioembolization
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: NRT6003-HCC-2022; CTR20230515 (Other Identifier: Center for Drug Evaluation, NMPA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Relevant results will be selectively disclosed in the future.

Drug and device information, study documents

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