This expansion cohort study will investigate the use of TATE in NET patients with liver-dominant metastatic disease. The phase I dose expansion HCC study with conventional 3+3 design established the appropriate intra-arterial (IA) dose of tirapazamine at 20 mg/m2 or 35 mg fixed dose. TATE will be performed by interventional radiologists. Tirapazamine at a fixed dose of 35 mg will be selectively delivered via catheter into tumor-feeding arteries followed by transarterial delivery of embolic agents (Lipiodol and Surgifoam). 

Stanford Investigator(s):

David Wang, MD

Eligibility

Inclusion Criteria:

• Patients with well-differentiated NET and liver-dominant metastatic disease with intrahepatic disease progression, regardless of primary tumor origin or tumor functional status. Patients may have extrahepatic lesions as long as the majority of the disease burden is intrahepatic.
• No limitation in hepatic lesion tumor size or number but the total volume of liver tumors cannot exceed 50% of the liver volume.
• Patients are allowed to have prior US Food and Drug Administration (FDA)-approved treatments, including systemic therapies, surgery, ablation, or transarterial therapies for the metastatic NET.
• Age 20 or higher, ECOG functional status 0-1, and with no known major cardiac, pulmonary, or renal dysfunction.
• Are candidates for TAE or TACE and without portal vein occlusion per treating interventional radiologists.
• ANC no less than 1000 /μL. Hemoglobin ≥ 9 gm/dL. Platelets no less than 50,000 /μL. Creatinine no more than 2.0 mg/dL. AST, ALT no more than 5X upper limit of normal. Bilirubin no more than 2.5 mg/dl. PT prolongation ≤ 4 sec above upper limit of normal.
• Woman of child-bearing potential (WOCBP) should use highly effective contraception during trial participation and for 6 months after the last dose of tirapazamine and men who are partners with WOCBP should use highly effective contraception, including barrier contraception, during trial participation and for 3 months after the last dose of tirapazamine.

Exclusion Criteria:

• Patients with O2 saturation less than 92% on room air.
• Patients with evidence of arterial insufficiency or microangiopathy due to any reason, such as diabetes, which could lead to distal extremity hypoxia, as evidenced by any gangrenous change in distal limbs or requiring resection for this reason.
• Patients with major gastrointestinal bleeding in the prior 2 months of enrollment.
• Patient on chronic anticoagulation therapy that cannot be temporarily suspended and is considered a risk for any invasive procedure such as TAE. Patients planned on receiving standard NET therapy (such as Sutent and radioactive Lutathera) during the study period, or are receiving other experimental agent should not enroll. Treatments for control the symptoms of carcinoid syndrome, such as octreotide or lanreotide are allowed.
• Pregnant and lactating woman.
• Patients with QTc interval >480 msec or those known to have congenital long QTc syndrome.
• Patients taking any medication (Appendix 1) that is known to prolong the QT interval and/or is associated with a risk of Torsades de Pointes will need to stop the medication with a washout period of 7 days prior to TATE.

Ages Eligible for Study

18 Years and older

Genders Eligible for Study

All