Clinical trial NCT06310590: Safety and Efficacy of TareSphere in Patients With Unresectable Hepatocellular Carcinoma
Official title: Study on the Safety and Effectiveness of NRT6003 Injection in Patients With Unresectable Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Unresectable Hepatocellular Carcinoma
Keywords: Selective internal radiation therapy
Yttrium-90
Transarterial Radioembolization;
Lead sponsor: Chengdu New Radiomedicine Technology Co. LTD.
Sponsor class: INDUSTRY
First posted: 2024-03-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events/ Severe adverse events
timeFrame: Up to 12 months
measure: Localized Objective response rates (ORR)
timeFrame: Up to 6 months (initial tumor assessment after administration)
Secondary outcomes:
measure: Hepatic time to progression (hTTP)
timeFrame: Up to 12 months
measure: Duration of response (DOR)
timeFrame: Up to 12 months
measure: Disease control rate (DCR)
timeFrame: Up to 12 months
measure: Time to progression (TTP)
timeFrame: Up to 12 months
measure: Progression Free Survival (PFS)
timeFrame: Up to 12 months
measure: Concentration of Alpha fetoprotein (AFP)
timeFrame: Up to 12 months
measure: Quality of life (QoL)
timeFrame: Up to 12 months
measure: Yttrium-90 distribution
timeFrame: Within 24 hours
measure: Resection rate of liver target lesions
timeFrame: Within 6 months after administration
measure: Radioactivity of Yttrium-90 for 9 participants, assessed by liquid scintillation counter
timeFrame: Within 168 hours
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Jinan University
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Nanjing
country: China
facility: Zhongda Hospital, Southeast University
state: Jiangsu
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Chongqing
country: China
facility: The Southwest Hospital of Army Medical University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shanghai
country: China
facility: The First Affiliated Hospital of Naval Medical University
city: Shanghai
country: China
facility: The Third Affiliated Hospital of Naval Medical University
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Insititute & Hospital
Study officials:
affiliation: Zhongda Hospital
name: Gaojun Teng, MD
role: PRINCIPAL_INVESTIGATOR
References: