Summary

for people ages 18-80 (full criteria)
at UC Irvine
study started
estimated completion:
Nadine Abi-Jaoudeh (uci)

Description

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.

Official Title

Phase IIA Single-Arm Study of Treatment of Patients With Advanced Liver Cancer With a Combination of TATE (Transarterial Tirapazamine Embolization) Followed by an Anti-PD-1 Monoclonal Antibody

Details

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 liver cancer derived from colorectal, gastric and NSCLC) 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 (either Nivolumab or Pembrolizumab per investigator decision). 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 and irRC for the non-TATE treated lesion, and compared with the historic RR of the PD-1 inhibitor in HCC (~16%) and mCRC (almost 0% for those without mismatch repair defect), advanced gastric cancer (15%) and metastatic NSCLC who failed to respond to an immune checkpoint inhibitor.

Keywords

Hepatocellular Carcinoma Colorectal Neoplasms Gastric Cancer Lung Cancer Colorectal cancer Immune checkpoint inhibitor Non-small cell lung cancer Carcinoma, Hepatocellular Stomach Neoplasms Liver Neoplasms Pembrolizumab Nivolumab Tirapazamine Antibodies, Monoclonal Opdivo Injectable Product or Keytruda Injectable Product Trans-arterial tirapazamine embolization NSCLC

Eligibility

You can join if…

Open to people ages 18-80

  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.

You CAN'T join if...

  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.

Location

  • University of California, Irvine accepting new patients
    Orange California 92868 United States

Lead Scientist

  • Nadine Abi-Jaoudeh (uci)
    Associate Clinical Professor, Radiological Sciences. Authored (or co-authored) 32 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Teclison Ltd.
ID
NCT03259867
Phase
Phase 2
Study Type
Interventional
Last Updated