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Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma

Primary Purpose

Unresectable Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Yttrium-90 carbon microspheres SIRT
Sponsored by
Zhongda Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Unresectable Hepatocellular Carcinoma focused on measuring SIRT

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Eastern Cooperative Oncology Group performance status ≤ 1; Expected survival time ≥ 3 months; Confirmed hepatocellular carcinoma based on EASL or AASLD guidelines; Without extrahepatic metastases, inoperable or refuse surgical resection; At least one well defined tumor (mRECIST 1.1); Tumor burden ≤ 50% of the total liver volume; Child-Pugh score ≤ 7; 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%; 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]; 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: With previous history of hepatic encephalopathy; 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; Percentage of hepatopulmonary shunt > 10%, or the single lung radiation absorbed dose > 30 Gy; With hepatic artery malformation and unable to intubate hepatic artery; Tumor thrombus in main portal vein; Have received radiotherapy or transcatheter arterial chemoembolization (patients who have received transcatheter arterial non-iodized oil chemoembolization are judged by researchers); The last anti-tumor treatment (surgery, chemotherapy, immunotherapy, targeted therapy) was less than 4 weeks before the drug administration; Clinical manifestations of portal hypertension, moderate-severe or refractory ascites, or decompensated liver cirrhosis; Participated in other trial within 1 month before yttrium-90 administration; Pregnant and lactating women; Serious infections in active stage or need systematic treatment; With positive results of HIV antibody test; The researchers judge that there is unresolved toxicity from previous treatment and will continue to exist, which may endanger the safety of patients; The researcher judged clinical or laboratory examination abnormality or other reasons; Extrahepatic disease or combined with other malignant tumors; Hepatic artery angiography and 99mTc MAA hepatic artery perfusion imaging demonstrate gastrointestinal shunts, which may not be remedied through vascular intervention techniques.

Sites / Locations

  • Gao-Jun TengRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Yttrium-90 carbon microspheres

Arm Description

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).

Outcomes

Primary Outcome Measures

Adverse events
Rates of adverse events
Objective response rates (ORR)
Liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)

Secondary Outcome Measures

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)
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.
Progression Free Survival Rate (PFS)
Survival probability of patients without imaging progression of liver target lesions
Time to progression (TTP)
Time with tumor progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Disease control rate (DCR)
Probability of tumor control
Duration of response (DOR)
Time without imaging progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Alpha fetoprotein (AFP)
The variation of AFP levels
Quality of life (QoL)
The variation of QoL with EORCT QLQ-C30
Resection rate of liver target lesions
Resection rate of liver target lesions

Full Information

First Posted
July 12, 2023
Last Updated
July 20, 2023
Sponsor
Zhongda Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05957640
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 5, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhongda Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable Hepatocellular Carcinoma
Keywords
SIRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Yttrium-90 carbon microspheres
Arm Type
Experimental
Arm Description
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).
Intervention Type
Combination Product
Intervention Name(s)
Yttrium-90 carbon microspheres SIRT
Intervention Description
Selective internal radiation therapy (SIRT) with yttrium-90 carbon microspheres
Primary Outcome Measure Information:
Title
Adverse events
Description
Rates of adverse events
Time Frame
Up to 24 months
Title
Objective response rates (ORR)
Description
Liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Time Frame
3 months after yttrium-90 injection
Secondary Outcome Measure Information:
Title
Hepatic time to progression (hTTP)
Description
Time to progression of liver target lesions, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Time Frame
Up to 24 months
Title
Yttrium-90 distribution
Description
Assessed by SPECT-CT imaging in the chest and upper abdomen, including extrahepatic shunts, intrahepatic distribution, and target lesion distribution as expected.
Time Frame
Within 24 hours
Title
Progression Free Survival Rate (PFS)
Description
Survival probability of patients without imaging progression of liver target lesions
Time Frame
3 months after yttrium-90 injection
Title
Time to progression (TTP)
Description
Time with tumor progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Time Frame
Up to 24 months
Title
Disease control rate (DCR)
Description
Probability of tumor control
Time Frame
Up to 24 months
Title
Duration of response (DOR)
Description
Time without imaging progression, evaluated by the investigator and independent image review committee respectively (CTCAE 5.0)
Time Frame
Up to 24 months
Title
Alpha fetoprotein (AFP)
Description
The variation of AFP levels
Time Frame
Up to 24 months
Title
Quality of life (QoL)
Description
The variation of QoL with EORCT QLQ-C30
Time Frame
Up to 24 months
Title
Resection rate of liver target lesions
Description
Resection rate of liver target lesions
Time Frame
Within 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Eastern Cooperative Oncology Group performance status ≤ 1; Expected survival time ≥ 3 months; Confirmed hepatocellular carcinoma based on EASL or AASLD guidelines; Without extrahepatic metastases, inoperable or refuse surgical resection; At least one well defined tumor (mRECIST 1.1); Tumor burden ≤ 50% of the total liver volume; Child-Pugh score ≤ 7; 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%; 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]; 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: With previous history of hepatic encephalopathy; 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; Percentage of hepatopulmonary shunt > 10%, or the single lung radiation absorbed dose > 30 Gy; With hepatic artery malformation and unable to intubate hepatic artery; Tumor thrombus in main portal vein; Have received radiotherapy or transcatheter arterial chemoembolization (patients who have received transcatheter arterial non-iodized oil chemoembolization are judged by researchers); The last anti-tumor treatment (surgery, chemotherapy, immunotherapy, targeted therapy) was less than 4 weeks before the drug administration; Clinical manifestations of portal hypertension, moderate-severe or refractory ascites, or decompensated liver cirrhosis; Participated in other trial within 1 month before yttrium-90 administration; Pregnant and lactating women; Serious infections in active stage or need systematic treatment; With positive results of HIV antibody test; The researchers judge that there is unresolved toxicity from previous treatment and will continue to exist, which may endanger the safety of patients; The researcher judged clinical or laboratory examination abnormality or other reasons; Extrahepatic disease or combined with other malignant tumors; Hepatic artery angiography and 99mTc MAA hepatic artery perfusion imaging demonstrate gastrointestinal shunts, which may not be remedied through vascular intervention techniques.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang, MD
Phone
+862583262224
Email
zhang_lei@seu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hai-Dong Zhu, MD
Phone
+862583262224
Email
zhuhaidong9509@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gao-Jun Teng, MD
Organizational Affiliation
Zhongda Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gao-Jun Teng
City
Nanjing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gao-Jun Teng, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Yttrium-90 Carbon Microspheres in Patients With Unresectable Hepatocellular Carcinoma

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