Combination of TATE and PD-1 Inhibitor in Liver Cancer

Phase 2

Recruiting

• Conditions: Hepatocellular Carcinoma; Gastric Cancer
• Interventions: Drug: Nivolumab Injectable Product; Combination Product: Trans-arterial tirapazamine embolization

• Registration Number: NCT03259867
• Lead Sponsor: Teclison Ltd.

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.

Study Timeline

• Study Start: 2017-07-01
• Study First Submitted: 2017-08-16
• Study First Submitted QC: 2017-08-22
• Study First Posted: 2017-08-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-22
• Primary Completion: 2025-12-31
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Advanced Hepatocellular carcinoma	Trans-arterial tirapazamine embolization	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	Trans-arterial tirapazamine embolization	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.
Advanced Hepatocellular carcinoma	Nivolumab Injectable Product	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	Nivolumab Injectable Product	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.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate	up to 24 months	Per RECIST 1.1 criteria

Secondary Outcome Measures

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

Trial Locations

Locations (3)

University of California, Irvine; 🇺🇸 Orange, California, United States

University of Oklahoma Health Science Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States