Combination of TATE and PD-1 Inhibitor in Liver Cancer (TATE-PD1)

Teclison

Status and phase: Enrolling; Phase 2

Conditions: Gastric Cancer; Hepatocellular Carcinoma

Treatments: Drug: Nivolumab Injectable Product; Combination Product: Trans-arterial tirapazamine embolization

Study type: Interventional

Funder types: Industry

Identifiers

NCT03259867

LT-004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 54 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

9. 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 2 patient groups

Advanced Hepatocellular carcinoma

Experimental group

Description:

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.

Treatment:

Combination Product: Trans-arterial tirapazamine embolization

Drug: Nivolumab Injectable Product

Metastatic Gastro-esophageal cancer

Experimental group

Description:

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.

Treatment:

Combination Product: Trans-arterial tirapazamine embolization

Drug: Nivolumab Injectable Product