Safety and Efficacy Study of Radioembolization in Combination With Durvalumab in Locally Advanced and Unresectable HCC

Study Overview
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Brief Summary
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Safety and Efficacy Study of Radioembolization with Yttrium-90 Microspheres in Combination with Durvalumab in Locally Advanced Hepatocellular Carcinoma

Detailed Description
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This is a single arm, open-label study to evaluate safety and efficacy of Radioembolization with Yttrium-90 Microspheres in Combination with Durvalumab in Locally Advanced and Unresectable Hepatocellular Carcinoma which to be implemented at a single site in Korea. Transarterial radioembolization (TARE) with yttrium-90 microspheres will be employed in combination with an intravenous (IV) durvalumab until PD. TARE will be performed before the first dose of durvalumab. Exploratory biomarker testing will be done on tumor tissues prior to treatment and plasma samples prior to treatment and at the time of PD.

Official Title
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A Single-arm, Open-label, Safety and Efficacy Study of Radioembolization With Yttrium-90 Microspheres in Combination With Durvalumab (MEDI4736) in Locally Advanced and Unresectable Hepatocellular Carcinoma (HCC) (SOLID)

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Durvalumab
* Radiation: Radioembolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with unequivocal HCC confirmed histologically or diagnosed radiologically Locally advanced HCC Must have at least 1 untreated measurable disease Child-Pugh score ≤7 points Adequate normal organ and marrow function. Exclusion Criteria: Eligible for potentially curative treatment (surgical resection, radio-frequency ablation or immediate liver transplantation) Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer, early gastric cancer, or other cancer for which the patient has been disease-free for at least five years. Evidence of extrahepatic metastasi(e)s, except for regional lymph node(s) involvement History of leptomeningeal carcinomatosis , History of active primary immunodeficiency Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. Exclusion Criteria Specific to Radioembolization: •The screening angiogram and technetium-99m macroaggregated albumin (99mTc-MAA) scan are used to determine lobar liver volume from CT or MR images, to identify vascular shunting to the GI tract requiring use of angiographic occlusion techniques and to determine the lung shunt fraction. Patients who are ineligible to radioembolization meeting the following criteria will not be included in the study. Additional patients will be screened to replace those patients. Deposition of yttrium-90 microspheres to the GI tract that cannot be corrected by placement of the catheter distal to collateral vessels or the application of standard angiographic techniques, such as coil embolization to prevent deposition of yttrium-90 microspheres in the GI tract. Exposure of radiation to the lungs exceeds 30 Gray (Gy) for a single infusion or 50 Gy cumulative for all infusions of yttrium-90 microspheres.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Transarterial radioembolization (TARE) with yttrium-90 microspheres will be employed in combination with an intravenous (IV) dose of 1500 mg durvalumab every 4 weeks (Q4W) until PD. TARE will be performed 1-2 weeks (7 to 14 days) before the first dose of durvalumab and a maximum of 2 more times during the treatment period, per Investigator discretion. If additional TARE is performed, the interval between additional TARE treatments and administration of durvalumab should be at least 1 week.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Yttrium-90 Microspheres in Combination with Durvalumab<br>Transarterial radioembolization (TARE) with yttrium-90 microspheres will be employed in combination with an intravenous (IV) dose of 1500 mg durvalumab every 4 weeks (Q4W) until PD. TARE will be performed 1-2 weeks (7 to 14 days) before the first dose of durvalumab and a maximum of 2 more times during the treatment period, per Investigator discretion. If additional TARE is performed, the interval between additional TARE treatments and administration of durvalumab should be at least 1 week. | Drug: Durvalumab<br>* Radioembolization with Yttrium-90 Microspheres<br>* Other names: Imfinzi®;Radiation: Radioembolization<br>* Radioembolization with Yttrium-90 Microspheres<br>* Other names: TheraSphere™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TTP | to evaluate time to progression (TTP) from enrolment using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). | From date of enrollment until the date of first documented progression, assessed up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OS | Overall Survival (OS) from first dose of study drug until the time of data cut-off, as determined by the Investigator. | From date of enrollment until the date of first documented progression, assessed up to 12 months | 
| ORR | Objective Response Rate (ORR) of Target Lesion(s) and Non-Target Lesion(s) | From date of enrollment until the date of first documented progression, assessed every 8 weeks up to 12 months. | 
| Number of participants with treatment-related adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Until 30 days after radioembolization with yttrium-90 microspheres or the last dose of durvalumab | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Durvalumab