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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Advanced Hepatocellular carcinoma | Experimental | 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. |
|
| Metastatic Gastro-esophageal cancer | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nivolumab Injectable Product | Drug | a PD-1 immune check inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | Per RECIST 1.1 criteria | up to 24 months |
| 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 |
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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.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ray Lee, MD. PhD | Contact | 8043341076 | ray.lee01@teclison.com | |
| Chiwei Lu, PhD. | Contact | chiwei.lu4@teclison.com |
| Name | Affiliation | Role |
|---|---|---|
| Nadine Abi-Jaoudeh, MD | UC Irvine Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Irvine | Recruiting | Orange | California | 92868 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35504436 | Background | Liu CH, Peng CM, Hwang JI, Liang PC, Chen PJ, Abi-Jaoudeh N, Giiang LH, Tyan YS. Phase I Dose-Escalation Study of Tirapazamine Chemoembolization for Unresectable Early- and Intermediate-Stage Hepatocellular Carcinoma. J Vasc Interv Radiol. 2022 Aug;33(8):926-933.e1. doi: 10.1016/j.jvir.2022.04.031. Epub 2022 Apr 30. | |
| 34041204 |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| D013274 | Stomach Neoplasms |
| D018450 | Disease Progression |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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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
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| Trans-arterial tirapazamine embolization | Combination Product | Embolization with Lipiodol and Gelfoam |
|
| 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 |
| University of Oklahoma Health Science Center | Recruiting | Oklahoma City | Oklahoma | 73104 | United States |
|
| Medical College of Wisconsin | Recruiting | Milwaukee | Wisconsin | 53226 | United States |
|
| Abi-Jaoudeh N, Dayyani F, Chen PJ, Fernando D, Fidelman N, Javan H, Liang PC, Hwang JI, Imagawa DK. Phase I Trial on Arterial Embolization with Hypoxia Activated Tirapazamine for Unresectable Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021 May 17;8:421-434. doi: 10.2147/JHC.S304275. eCollection 2021. |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D013272 | Stomach Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |