Ablative Radioembolization as a Spearhead Treatment for Locally Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— RESOLVE  

Official title:

An Open-label, Prospective, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Ablative Radioembolization Using Yttrium-90 Glass Microspheres in Patients With Locally-advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06166576
• Other study ID #: D-2306-207-1446
• Status: Recruiting
• Phase: Phase 2
• Start date: November 20, 2023
• Est. completion date: November 30, 2027

Study information

• Verified date: March 2024
• Source: Seoul National University Hospital
• Contact: Jin Woo Choi, MD, PhD
• Phone: +82-220722584
• Email: jwchoi.med[@]snu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The RESOLVE trial, an open-label, single-arm, multi-center study, aims to assess the efficacy and safety of ablative radioembolization using TheraSphere Yttrium-90 microspheres. This trial specifically targets patients diagnosed with hepatocellular carcinoma accompanied by localized portal vein tumor thrombosis (Vp1-Vp3) and who maintain good liver function.

Description:

Patients diagnosed with unilobar hepatocellular carcinoma and localized portal vein tumor thrombosis (Vp1-Vp3), who also exhibit good liver function, will undergo ablative radioembolization with a dose exceeding 205 Gy to the tumor using TheraSphere glass microspheres. These patients will be monitored over a two-year period to evaluate their clinical course, treatment outcomes, and safety.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 30, 2027
• Est. primary completion date: November 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Adults aged 18 and over

2. Patients diagnosed with unilobar hepatocellular carcinoma, either histologically and/or radiologically (LI-RADS 4 or 5)

3. Patients with at least one measurable lesion greater than 10 mm on dynamic contrast-enhanced CT or MRI

4. Patients with localized portal vein invasion limited in one lobe (Vp1-3) on dynamic contrast-enhanced CT or MRI

5. Patients with no extrahepatic metastasis on lung CT and contrast-enhanced abdominal CT or MRI

6. Patients with no prior treatment for liver cancer

7. Child-Pugh class A

8. Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less

9. Patients without serious dysfunction of major organs, as indicated by blood tests conducted within one month of study enrollment

1. Leukocytes = 2,500/µL and = 12,000/µL

2. Absolute neutrophil count = 1,500/mm^3

3. Hemoglobin = 8.0 g/dL (transfusions allowed to meet this criterion)

4. Total bilirubin = 3.0 mg/dL

5. Platelets = 50,000/µL

6. For patients not on anticoagulants, INR = 2.0

7. AST = 200 IU/L (i.e., = 5X upper normal limit)

8. ALT = 200 IU/L (i.e., = 5X upper normal limit)

9. ALP = 575 IU/L (i.e., = 5X upper normal limit)

10. Creatinine = 2.0 mg/dL

10. Patients with a life expectancy of more than 3 months

11. Patients who have fully understood the clinical trial and given written consent

12. Female patients of childbearing age confirmed not to be pregnant

Exclusion Criteria:

1. Patients unsuitable for ablative radioembolization as per the pre-test with macro-aggregated albumin labeled with technetium-99 (99mTc-MAA) for radioembolization.

1. Cases where, according to multi-compartment Medical Internal Radiation Dose method, delivering 205 Gy of radiation to the tumor exceeds an estimated lung dose of 25 Gy.

2. Cases with severe hepatic artery-portal vein shunting leading to expected irradiation of the non-tumorous opposite lobe.

2. Patients whose volume of non-tumorous liver not included in the treatment area is less than 30% of the total non-tumorous liver volume.

3. Patients with hepatic vein or bile duct invasion as seen on dynamic contrast-enhanced CT or MRI.

4. Patients scheduled to use immunotherapy regardless of the response to radioembolization.

5. Patients who had active cancer within two years prior to joining the clinical trial.

6. Patients who have undergone surgery or procedures related to the bile duct.

7. Pregnant or breastfeeding women.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Procedure:
• Ablative radioembolization
The interventional radiologist utilizes a pre-test with 99mTc-MAA SPECT-CT and cone-beam CT for procedural planning. For tumors confined to a single segment, the treatment area is planned to receive a radiation dose of over 400 Gy using the single-compartment MIRD technique. For tumors extending beyond a single segment, the multi-compartment MIRD technique is used to plan a radiation dose of 700 Gy (± 20%) to the tumor. The upper limit for the estimated lung dose is set at 25 Gy, and the upper limit for the perfused non-tumoral liver dose is 250 Gy. In cases where tumors extending beyond a single segment cannot receive the planned dose of 700 Gy (± 20%) due to limits on lung or normal liver dose, the plan is adjusted to deliver the maximum dose to the tumor within the permissible range for lung and normal liver doses. Radioembolization is typically performed in a single session, and any methods not mentioned here should follow the instructions for use of TheraSphere.

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pre-treatment dosimetry based on 99mTc-MAA SPECT-CT		Baseline
Other	Post-treatment dosimetry based on Y90 PET-CT		Within two days after the procedure
Primary	Objective response rate according to localized mRECIST	The number of patients with partial or complete response as the best local response divided by the total number of participants	Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Primary	Duration of response according to localized mRECIST	The time from first documentation of partial or complete response to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer treatment, whichever comes first	Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Objective response rate according to mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Duration of response according to mRECIST		Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	2-year restricted mean duration of response according to localized mRECIST and mRECIST		Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months after the initial treatment
Secondary	Complete response rate according to localized mRECIST and mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Duration of complete response according to localized mRECIST and mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	2-year restricted mean DoCR (RMDoCR) according to localized mRECIST and mRECIST		Time of complete response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months after the initial treatment
Secondary	Best response within 2-years according to localized mRECIST and mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Time to best response according to localized mRECIST and mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Time to progression according to localized mRECIST and mRECIST		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Overall survival		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	2-year restricted mean survival time of overall survival		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or 24 months the initial treatment
Secondary	Progression-free survival		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Hepatic progression-free survival		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Pathological necrosis rate (%) after curative resection or liver transplantation		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Time to subsequent HCC treatment		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Reason for subsequent HCC treatment		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Rate for conversion to curative resection and liver transplantation		Time of treatment up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (24 months after the last patient is enrolled)
Secondary	Adverse event and serious adverse event	Common Terminology Criteria for Adverse Events v5.0	Time of treatment up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Secondary	Changes in Child-Pugh class		Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Secondary	Changes in ALBI (albumin-bilirubin) grade		Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Secondary	Changes in MELD (Model for end-stage liver disease) score		Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first
Secondary	Changes in ECOG (Eastern Cooperative Oncology Group) performance status scale	0 (fully active) to 5 (dead)	Baseline up to 90 days after the initial treatment or subsequent anticancer treatment, whichever comes first