Combination of TATE and PD-1 Inhibitor in Liver Cancer

NCT ID: NCT03259867

Last Updated: 2024-11-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2025-12-31

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.

Conditions

Hepatocellular Carcinoma; Gastric Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Advanced Hepatocellular carcinoma

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.

Group Type: EXPERIMENTAL

Nivolumab Injectable Product

Intervention Type: DRUG

a PD-1 immune check inhibitor

Trans-arterial tirapazamine embolization

Intervention Type: COMBINATION_PRODUCT

Embolization with Lipiodol and Gelfoam

Metastatic Gastro-esophageal cancer

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.

Group Type: EXPERIMENTAL

Nivolumab Injectable Product

Intervention Type: DRUG

a PD-1 immune check inhibitor

Trans-arterial tirapazamine embolization

Intervention Type: COMBINATION_PRODUCT

Embolization with Lipiodol and Gelfoam

Interventions

Nivolumab Injectable Product

a PD-1 immune check inhibitor

Intervention Type: DRUG

Trans-arterial tirapazamine embolization

Embolization with Lipiodol and Gelfoam

Intervention Type: COMBINATION_PRODUCT

Other Intervention Names

OPDIVO

Eligibility Criteria

Inclusion 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.

Exclusion Criteria

Patients with a history of major autoimmune disorders excluded.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teclison Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nadine Abi-Jaoudeh, MD

Role: PRINCIPAL_INVESTIGATOR

UC Irvine Medical Center

Locations

University of California, Irvine

Orange, California, United States

Site Status: RECRUITING

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ray Lee, MD. PhD

Role: CONTACT

ray.lee01@teclison.com

8043341076

Chiwei Lu, PhD.

Role: CONTACT

chiwei.lu4@teclison.com

Facility Contacts

Miranda Duron

Role: primary

Role: backup

mnduron@hs.uci.edu

Melissa Yarbrough, RN

Role: primary

melissa-yarbrough@ouhsc.edu

Barbara Dion

Role: primary

badion@mcw.edu

References

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.

Reference Type: BACKGROUND

PMID: 35504436 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 34041204 (View on PubMed)

Other Identifiers

LT-004

Identifier Type: -

Identifier Source: org_study_id