Clinical trial NCT05957640: Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma
Official title: Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma: A Multicentre, Prospective, Open-label, Single-arm Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Unresectable Hepatocellular Carcinoma
Keywords: SIRT
Lead sponsor: Zhongda Hospital
Sponsor class: OTHER
First posted: 2023-07-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 24 months
measure: Objective response rates (ORR)
timeFrame: 3 months after yttrium-90 injection
Secondary outcomes:
measure: Hepatic time to progression (hTTP)
timeFrame: Up to 24 months
measure: Yttrium-90 distribution
timeFrame: Within 24 hours
measure: Progression Free Survival Rate (PFS)
timeFrame: 3 months after yttrium-90 injection
measure: Time to progression (TTP)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: Up to 24 months
measure: Duration of response (DOR)
timeFrame: Up to 24 months
measure: Alpha fetoprotein (AFP)
timeFrame: Up to 24 months
measure: Quality of life (QoL)
timeFrame: Up to 24 months
measure: Resection rate of liver target lesions
timeFrame: Within 6 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Gao-Jun Teng
Study officials:
affiliation: Zhongda Hospital
name: Gao-Jun Teng, MD
role: PRINCIPAL_INVESTIGATOR
References: