Combination of TATE and PD-1 Inhibitor in Liver Cancer

Hepatocellular Carcinoma Clinical Trial

— TATE-PD1  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03259867
• Other study ID #: LT-004
• Status: Recruiting
• Phase: Phase 2
• Start date: July 1, 2017
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: Teclison Ltd.
• Contact: Ray Lee, MD. PhD
• Phone: 8043341076
• Email: ray.lee01[@]teclison.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Gastric Cancer
• Hepatocellular Carcinoma
• Liver Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• Nivolumab Injectable Product
a PD-1 immune check inhibitor

Combination Product:
• Trans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam

Locations

Country	Name	City	State
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Oklahoma Health Science Center	Oklahoma City	Oklahoma
United States	University of California, Irvine	Orange	California

Sponsors (1)

Lead Sponsor	Collaborator
Teclison Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Per RECIST 1.1 criteria	up to 24 months
Secondary	Duration of Response	From the date of image-demonstrated response to the date of progression	up to 24 months
Secondary	Time to Progression	From randomization to disease progression or death	up to 24 months
Secondary	Progression Free Survival	From randomization to disease progression or death	up to 24 months
Secondary	Overall survival	From randomization to death	through study completion, an average of 3 years