Combination of TATE and PD-1 Inhibitor in Liver Cancer

Study Overview
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Brief Summary
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This is a multi-center, open-label phase IIA study that investigates the preliminary efficacy of Trans-arterial Tirapazamine Embolization (TATE) treatment of liver cancer followed by a PD-1 checkpoint inhibitor (nivolumab). Patients with two types of cancers will be enrolled, advanced hepatocellular carcinoma (HCC),and metastatic gastric cancer. All enrolled patients need to have liver lesions and have progressed on a prior immune checkpoint inhibitor.

Detailed Description
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The goal of the study is to investigate whether tumor necrosis induced by Trans-arterial Tirapazamine Embolization (TATE) treatment can boost anti-tumor immunity and enhance the therapeutic efficacy of immune checkpoint inhibitor. Patients with advanced liver cancers (primary HCC or metastatic gastric cancer) who have progressed on a prior immune checkpoint inhibitor will be enrolled in the study. Liver lesions will be treated with up to 4 TATE treatments for optimal debulking, which also serve as a vaccination process toward tumor. Lesion not treated with TATE will be used for monitoring the response toward a PD-1 inhibitor (Nivolumab) for abscopal effect. If a patient subsequently develops an escape to the PD-1 inhibitor, patient can have another 2 TATE treatments of the escaped tumor lesion. Dosing of the PD-1 inhibitor is per standard FDA-approved dosing schedule and continues until progressive disease. The efficacy will be assessed by the response rate (RR) using RECIST.

Official Title
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Phase IIA Single-Arm Study of Treatment of Patients With Advanced Liver Cancer With a Combination of TATE (Transarterial Tirapazamine Embolization) Followed by an Anti-PD-1 Monoclonal Antibody

Conditions
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Hepatocellular Carcinoma, Gastric Cancer

Intervention / Treatment
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* Drug: Nivolumab Injectable Product
* Combination Product: Trans-arterial tirapazamine embolization


Participation Criteria
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Eligibility Criteria
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Patients with a confirmed diagnosis of (1) advanced HCC or (2) metastatic gastric cancer. Patients between ages 18 and 80 If HCC patients, they should have progressive disease (PD) on an immune therapy for advanced HCC. For patients with metastatic gastric cancer, they should have failed at least one line of systemic chemotherapy and an immune checkpoint inhibitor. Patients with liver tumor lesions with at least one with a diameter of 2 cm or bigger, which is amendable for (super-)selective TATE as the target lesion. ECOG score 2 or less Child-Pugh scores 5-7 for HCC patients All prior chemotherapy at least 4 weeks prior to study treatment. Immunotherapy not subject to this limitation. No major GI bleeding in the prior 2 months. 8. Hgb>=8, platelet >= 50,000, Cr =< 2, AST and ALT < 10 X ULN, t-Bilirubin < 3, 9. Patients with a history of major autoimmune disorders excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: One arm for advanced HCC, and one for second line metastatic gastro-esophageal cancer . All enrolled patients will receive the same treatment with TATE and a PD-1 inhibitor (nivolumab) until disease progression
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Advanced Hepatocellular carcinoma<br>PD-1 inhibitor (Nivolumab 360 mg Q3W IV ) starts at day 1, and continues until progression. TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization. | Drug: Nivolumab Injectable Product<br>* a PD-1 immune check inhibitor<br>* Other names: OPDIVO;Combination Product: Trans-arterial tirapazamine embolization<br>* Embolization with Lipiodol and Gelfoam<br>|
| Experimental: Metastatic Gastro-esophageal cancer<br>PD-1 inhibitor (Nivolumab 360 mg Q3W IV) starts at day 1, and continues until progression. TATE treatment starts at day 8 for debulking up to 4 cycles. If escape lesion appears, two more TATE treatments can be given. Tirapazamine dose at 35 mg flat dose given before embolization. | Drug: Nivolumab Injectable Product<br>* a PD-1 immune check inhibitor<br>* Other names: OPDIVO;Combination Product: Trans-arterial tirapazamine embolization<br>* Embolization with Lipiodol and Gelfoam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Per RECIST 1.1 criteria | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response | From the date of image-demonstrated response to the date of progression | up to 24 months | 
| Time to Progression | From randomization to disease progression or death | up to 24 months | 
| Progression Free Survival | From randomization to disease progression or death | up to 24 months | 
| Overall survival | From randomization to death | through study completion, an average of 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Immune checkpoint inhibitor, Gastric cancer, Progression