Combination of TATE and PD-1 Inhibitor in Liver Cancer

NCT03259867 | Recruiting Phase 2 FDA Drug

• 1 other identifier: LT-004
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatocellular Carcinoma; Gastric Cancer

Keywords

Hepatocellular carcinoma; Immune checkpoint inhibitor; Gastric cancer; Progression

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Per RECIST 1.1 criteria

  up to 24 months

Secondary Outcomes (4)

• Duration of Response

  up to 24 months

• Time to Progression

  up to 24 months

• Progression Free Survival

  up to 24 months

• Overall survival

  through study completion, an average of 3 years

Study Arms (2)

Advanced Hepatocellular carcinoma

EXPERIMENTAL

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.

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

Metastatic Gastro-esophageal cancer

EXPERIMENTAL

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.

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

Interventions

Nivolumab Injectable Product DRUG

a PD-1 immune check inhibitor

Also known as: OPDIVO

Advanced Hepatocellular carcinoma; Metastatic Gastro-esophageal cancer

Trans-arterial tirapazamine embolization COMBINATION_PRODUCT

Embolization with Lipiodol and Gelfoam

Advanced Hepatocellular carcinoma; Metastatic Gastro-esophageal cancer

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Teclison Ltd.: lead

Study Sites (3)

University of California, Irvine

Orange, California, 92868, United States

RECRUITING

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 35504436 BACKGROUND

• 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.

  PMID: 34041204 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Stomach Neoplasms; Disease Progression

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Nadine Abi-Jaoudeh, MD

  UC Irvine Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ray Lee, MD. PhD

CONTACT

8043341076; ray.lee01@teclison.com

Chiwei Lu, PhD.

CONTACT

chiwei.lu4@teclison.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 16, 2017
• First Posted: August 24, 2017
• Study Start: July 1, 2017
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)