Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma

Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma: A Multicentre, Prospective, Open-label, Single-arm Trial

To evaluate the efficacy and safety of yttrium-90 carbon microspheres in patients with unresectable hepatocellular carcinoma

Study Overview

• Status: Recruiting
• Conditions: Unresectable Hepatocellular Carcinoma
• Intervention / Treatment: Combination product: Yttrium-90 carbon microspheres SIRT

Detailed Description

The efficacy and safety of yttrium-90 carbon microspheres in patients with unresectable hepatocellular carcinoma remain unknown. This multicentre, prospective, open-label, single-arm trial is designed to evaluate the safety and efficacy of yttrium-90 carbon microspheres in patients with hepatocellular carcinoma. The primary endpoints are safety and local objective response rate of liver target lesions. While the secondary endpoints include the time to progression, progression-free survival rates, disease control rates, duration of response, quality of life and the distribution characteristics of yttrium-90 carbon microspheres.

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

Contacts and Locations

• Study Contact: Name: Hai-Dong Zhu, MD; Phone Number: +862583262224; Email: zhuhaidong9509@163.com
• Study Contact Backup: Name: Lei Zhang, MD; Phone Number: +862583262224; Email: zhang_lei@seu.edu.cn

Study Locations

• China
  • Nanjing, China
    • Recruiting
    • Gao-Jun Teng
    • Contact: Gao-Jun Teng, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Eastern Cooperative Oncology Group performance status ≤ 1;
2. Expected survival time ≥ 3 months;
3. Confirmed hepatocellular carcinoma based on EASL or AASLD guidelines;
4. Without extrahepatic metastases, inoperable or refuse surgical resection;
5. At least one well defined tumor (mRECIST 1.1);
6. Tumor burden ≤ 50% of the total liver volume;
7. Child-Pugh score ≤ 7;
8. Adequate organ function: # Blood routine [no blood transfusion or colony-stimulating factor (G-CSF) treatment within 14 days]: absolute neutrophil count ≥ 1.5 × 109/L; platelet ≥ 75 × 109/L; hemoglobin ≥ 90 g/ L; # Liver function: total bilirubin ≤ 2 times upper limit of normal (ULN); alanine transaminase and aspartate aminotransferase ≤ 5. 0 ULN; alkaline phosphatase ≤ 2.5 ULN; Albumin > 30 g/L; # Renal function: Cr ≤ 1.5 ULN; creatinine clearance ≥ 50 mL/min (calculated according to Cockcroft-Gault formula); # Coagulation function: international normalized ratio, prothrombin time and activated partial thromboplastin time were less than 1.5 ULN; # Cardiovascular function: left ventricular ejection fraction ≥ 50%;
9. According to CTCAE 5.0 standard, all adverse events of previous systematic anti-cancer treatment have recovered to baseline or ≤ 1 grade, [except for the following: neuropathy induced by previous anticancer treatment is stable (≤ 2 grade) and hair loss];
10. Women and men of childbearing age must agree to take strict and effective contraceptive measures during the study period and within 6 m after the end of the trial. Men are forbidden to donate sperm. The pregnancy test results of female patients of childbearing age during the screening period and within 24 hours before administration must be negative.

Exclusion Criteria:

1. With previous history of hepatic encephalopathy;
2. Severe pulmonary insufficiency (forced expiratory volume at one second / forced vital capacity < 50% or forced expiratory volume at one second /predicting value < 50% or maximum volume per minute < 50 L/min);Obvious chronic obstructive pulmonary disease or interstitial pneumonia;
3. Percentage of hepatopulmonary shunt > 10%, or the single lung radiation absorbed dose > 30 Gy;
4. With hepatic artery malformation and unable to intubate hepatic artery;
5. Tumor thrombus in main portal vein;
6. Have received radiotherapy or transcatheter arterial chemoembolization (patients who have received transcatheter arterial non-iodized oil chemoembolization are judged by researchers);
7. The last anti-tumor treatment (surgery, chemotherapy, immunotherapy, targeted therapy) was less than 4 weeks before the drug administration;
8. Clinical manifestations of portal hypertension, moderate-severe or refractory ascites, or decompensated liver cirrhosis;
9. Participated in other trial within 1 month before yttrium-90 administration;
10. Pregnant and lactating women;
11. Serious infections in active stage or need systematic treatment;
12. With positive results of HIV antibody test;
13. The researchers judge that there is unresolved toxicity from previous treatment and will continue to exist, which may endanger the safety of patients;
14. The researcher judged clinical or laboratory examination abnormality or other reasons;
15. Extrahepatic disease or combined with other malignant tumors;
16. Hepatic artery angiography and 99mTc MAA hepatic artery perfusion imaging demonstrate gastrointestinal shunts, which may not be remedied through vascular intervention techniques.

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: Yttrium-90 carbon microspheres; Single dose of yttrium-90 carbon microspheres injection. Patients will be assessed by SPECT-CT imaging within 24 hours for yttrium-90 distribution in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.Six Patients will be tested for the radioactivity of yttrium-90 in blood, urine, and feces (if available).

Combination product: Yttrium-90 carbon microspheres SIRT; Selective internal radiation therapy (SIRT) with yttrium-90 carbon microspheres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Rates of adverse events	Up to 24 months
Objective response rates (ORR)	Liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)	3 months after yttrium-90 injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	Probability of tumor control	Up to 24 months
Hepatic time to progression (hTTP)	Time to progression of liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)	Up to 24 months
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
Progression Free Survival Rate (PFS)	Survival probability of patients without imaging progression of liver target lesions	3 months after yttrium-90 injection
Time to progression (TTP)	Time with tumor progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)	Up to 24 months
Duration of response (DOR)	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)	Up to 24 months
Alpha fetoprotein (AFP)	The variation of AFP levels	Up to 24 months
Quality of life (QoL)	The variation of QoL with EORCT QLQ-C30	Up to 24 months
Resection rate of liver target lesions	Resection rate of liver target lesions	Within 6 months

Collaborators and Investigators

• Sponsor: Zhongda Hospital
• Investigators: Principal Investigator: Gao-Jun Teng, MD, Zhongda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2023
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: July 12, 2023
• First Submitted That Met QC Criteria: July 20, 2023
• First Posted (Estimated): July 24, 2023

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: SIRT
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CHANCE2303-NRT6003-HCC

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: No
• Studies a U.S. FDA-regulated device product: No