Gastric Cancer, Hepatocellular Carcinoma
Conditions
Keywords
Hepatocellular carcinoma, Immune checkpoint inhibitor, Gastric cancer, Progression
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.
Interventions
a PD-1 immune check inhibitor
COMBINATION_PRODUCTTrans-arterial tirapazamine embolization
Embolization with Lipiodol and Gelfoam
Sponsors
Teclison Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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. Patients with a history of major autoimmune disorders excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | up to 24 months | Per RECIST 1.1 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall survival | through study completion, an average of 3 years | From randomization to death |
Countries
United States
Contacts
CONTACTRay Lee, MD. PhD
CONTACTChiwei Lu, PhD.
PRINCIPAL_INVESTIGATORNadine Abi-Jaoudeh, MD
UC Irvine Medical Center
Outcome results
None listed