Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma

Phase 1

Recruiting

• Conditions: Unresectable Hepatocellular Carcinoma
• Interventions: Combination Product: Yttrium-90 carbon microspheres SIRT

• Registration Number: NCT05957640
• Lead Sponsor: Zhongda Hospital

Brief Summary

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

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 Timeline

• Study Start: 2023-05-05
• Status Verified: 2023-07
• Study First Submitted: 2023-07-12
• Study First Submitted QC: 2023-07-20
• Last Update Submitted: 2023-07-20
• Study First Posted: 2023-07-24
• Last Update Posted: 2023-07-24
• Primary Completion: 2025-05-31
• Study Completion: 2025-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Yttrium-90 carbon microspheres	Yttrium-90 carbon microspheres SIRT	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Resection rate of liver target lesions	Within 6 months	Resection rate of liver target lesions
Hepatic time to progression (hTTP)	Up to 24 months	Time to progression of liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Alpha fetoprotein (AFP)	Up to 24 months	The variation of AFP levels
Progression Free Survival Rate (PFS)	3 months after yttrium-90 injection	Survival probability of patients without imaging progression of liver target lesions
Duration of response (DOR)	Up to 24 months	Time without imaging progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Yttrium-90 distribution	Within 24 hours	Assessed by SPECT-CT imaging in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.
Time to progression (TTP)	Up to 24 months	Time with tumor progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Quality of life (QoL)	Up to 24 months	The variation of QoL with EORCT QLQ-C30
Disease control rate (DCR)	Up to 24 months	Probability of tumor control

Trial Locations

Locations (1)

Gao-Jun Teng; 🇨🇳 Nanjing, China