Safety and Efficacy of NRT6003 in Patients With Unresectable Hepatocellular Carcinoma

Unresectable Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06310590
• Other study ID #: NRT6003-HCC-2022
• Secondary ID: CTR20230515
• Status: Recruiting
• Phase: Phase 1
• Start date: August 8, 2023
• Est. completion date: October 31, 2025

Study information

• Verified date: December 2023
• Source: Chengdu New Radiomedicine Technology Co. LTD.
• Contact: Gaojun Teng
• Phone: +8602583272084
• Email: zdyyjgb[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

The efficacy and safety of Yttrium-90 carbon microspheres in patients with unresectable HCC remain 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Aged 18 to 80 and signed informed consent;

2. Diagnosed as hepatocellular carcinoma clinically, by imaging and/or pathology based on National Health Commission guideline (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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Unresectable Hepatocellular Carcinoma

Intervention

Drug:
• NRT6003 Injection
Selective internal radiation therapy (SIRT) with Yttrium-90 carbon microspheres

Locations

Country	Name	City	State
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The Southwest Hospital of Army Medical University	Chongqing
China	Fujian Provincial Cancer Hospital	Fuzhou	Fujian
China	The First Affiliated Hospital of Jinan University	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Anhui Provincial Hospital	Hefei	Anhui
China	The Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	Zhongda Hospital, Southeast University	Nanjing	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai
China	The First Affiliated Hospital of Naval Medical University	Shanghai
China	The Third Affiliated Hospital of Naval Medical University	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Insititute & Hospital	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chengdu New Radiomedicine Technology Co. LTD.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events/ Severe adverse events	Occurrence of adverse events/severe adverse events	Up to 12 months
Primary	Localized Objective response rates (ORR)	Liver target lesions, evaluated based on the mRECIST criteria	Up to 6 months (initial tumor assessment after administration)
Secondary	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
Secondary	Duration of response (DOR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Secondary	Disease control rate (DCR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Secondary	Time to progression (TTP)	Time with tumor progression, evaluated by the investigator and independent image review committee respectively (mRECIST)	Up to 12 months
Secondary	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
Secondary	Concentration of Alpha fetoprotein (AFP)	The variation of AFP levels	Up to 12 months
Secondary	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
Secondary	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
Secondary	Resection rate of liver target lesions	Resection rate of liver target lesions	Within 6 months after administration
Secondary	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