Clinical trial NCT03259867: Combination of TATE and PD-1 Inhibitor in Liver Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Gastric Cancer
Keywords: Hepatocellular carcinoma
Immune checkpoint inhibitor
Gastric cancer
Progression
Lead sponsor: Teclison Ltd.
Sponsor class: INDUSTRY
First posted: 2017-08-24
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 1. Patients with a confirmed diagnosis of (1) advanced HCC or (2) metastatic gastric cancer.
2. Patients between ages 18 and 80
3. 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.
4. 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.
5. ECOG score 2 or less
6. Child-Pugh scores 5-7 for HCC patients
7. All prior chemotherapy at least 4 weeks prior to study treatment. Immunotherapy not subject to this limitation.
8. 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: up to 24 months
Secondary outcomes:
measure: Duration of Response
timeFrame: up to 24 months
measure: Time to Progression
timeFrame: up to 24 months
measure: Progression Free Survival
timeFrame: up to 24 months
measure: Overall survival
timeFrame: through study completion, an average of 3 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: UC Irvine Medical Center
name: Nadine Abi-Jaoudeh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.