Combination of TATE and PD-1 Inhibitor in Liver Cancer

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a single 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 (either nivolumab or pembrolizumab). Patients with four types of cancers will be enrolled, hepatocellular carcinoma (HCC), metastatic colorectal cancer (mCRC), metastatic gastric cancer and advanced non-small cell lung cancer. All enrolled patients need to have liver lesions.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Teclison Ltd.
• Treatments: Antibodies, Monoclonal; Nivolumab; Pembrolizumab; Tirapazamine

Criteria

Inclusion Criteria:

1. Patients with either a confirmed diagnosis of (1) metastatic colorectal cancer in liver based on histopathology of either a prior resection of primary lesion or a biopsied liver metastatic lesion; (2) advanced HCC (BCLC-stage C) with a characteristic 3 or 4-phase CT or dynamic contrast enhanced MRI finding showing arterial uptake followed by "washout" of contrast in the venous-delayed phases per American Association for the Study of Liver Disease (AASLD) criteria; (3) metastatic gastric cancer; (4) metastatic NSCLC without EGFR or ALK mutation.

2. Patients between ages 18 and 80

3. If HCC patients, they should have progressive disease (PD) on intolerant of or refusing sorafenib. If mCRC, they should have received at least one regimen of 5-fluouracil based systemic chemotherapy such as FOLFOX, FOLFIRI, CAPOX, or XELOX, with or without a VEGF or EGFR receptor inhibitor. For patients with metastatic gastric cancer, they should have failed at least one line of systemic chemotherapy. For patients with NSCLC, they should have been treated with a PD-1 inhibitor (either with or without chemotherapy) for at least 4 months but are not able to achieve a response.

4. Patients with at least two 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. Alternatively, patients with one intra-hepatic lesion of 2 cm or bigger and exhapetic lesion(s) are also acceptable.

5. ECOG score 2 or less

6. Child-Pugh scores 5-7

7. Patients should have measurable disease by contrast CT or contrast-enhanced MRI.

8. All prior chemotherapy must be at least 4 weeks prior to TATE and free from treatment-related toxicity. No gap is needed for prior PD-1 checkpoint inhibitors in NSCLC patients.

9. Patients have normal organ function: Hemoglobin ≥ 8.5 gm/dL, Platelets ≥ 50,000 /µL, Creatinine ≤ 2 mg/dL, AST and ALT < 10 X upper normal limit of the current institution; bilirubin < 3.0 mg/dL

10. Patients are able to understand and willing to sign the informed consent.

11. Men and women of child-bearing age need to commit to using two methods of contraception simultaneously to avoid pregnancy.

Exclusion Criteria:

1. Patients who have had a liver or any organ transplantation

2. Patients who take any immune or bone marrow suppressive agents including any systemic corticosteroid that exceed an equivalent of 10 mg prednisone per day within 2 weeks from the study treatment. Inhalation or topical steroids are allowed.

3. Patients who have received any checkpoint inhibitor, including ipilimumab, nivolumab, pembrolizumab or others.

4. Patients who have major medical problems such as severe cardiac, pulmonary (COPD requiring constant oxygen), or non-healing ulceration.

5. Patients with a history of autoimmune disease (e.g., rheumatoid arthritis, Addison's syndrome, multiple sclerosis, uveitis, systemic lupus erythematosus or Wegener's granulomatosis). Patients with vitiligo or alopecia are allowed. Patients with Graves disease or psoriasis not requiring systemic treatment within the past 2 years are allowed.

6. Patients who have any clinical evidence of hypoxia with O2 saturation less than 92% on room air.

7. Patients with evidence of significant arterial insufficiency or microangiopathy in any organ due to any reason, which could lead to distal extremity hypoxia, as evidenced by any gangrenous change in distal limbs or requiring resection for this reason.

8. Patients with major gastrointestinal bleeding in the prior 2 months of enrollment.

9. Patients who are pregnant or lactating.

10. Patients with QTc interval > 480 msec or those known to have congenital long QTc syndrome.

11. Patients who have received live, attenuated vaccine within 28 days prior to the first dose of PD-1 inhibitor.