Selective Intra-arterial Injection of PRRT in Neuroendocrine Tumor Patients With Liver Metastases

[90]Yttrium-DOTATOC is a radioactive drug used for peptide receptor radionuclide therapy
(PRRT). In other studies, 90Y-DOTATOC has been administered through a vein (IV) to target
somatostatin receptor positive tumor tissue. The DOTATOC identifies the tumor through the
somatostatin receptor and links to it, attaching the radioactive molecule 90Yttrium to the
malignant cell.

This study expands the initial work to examine if administering the drug 90Y-DOTATOC directly
to the liver is safe for patients with neuroendocrine tumors whose disease has spread to
their tumor. We don't know how of the 90Y-DOTATOC is safe to administer. We want to learn
what the maximum safe dose is and what the side effects are related to that dose.

Inclusion Criteria:

- Ability to understand and the willingness to provide informed consent

- Pathologically well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2).

- Primary tumor location should be known or believed to be midgut.

- At least one tumor in the liver that is positive with [68]Ga-DOTATATE (NETSPOT).
Imaging must be performed within the past 6 months.

- Liver lesions not amendable to other therapies (surgery, ablation) and have progressed
after treatment with octreotide/lanreotide and/or other treatments. (everolimus,
sunitinib).

- Karnofsky performance status of at least 70

- Absolute neutrophil count of at least 1,000 cells/mm3

- Platelet count of at least 90,000 cells / mm3

- Total bilirubin ≤ 2 x the upper limit of normal when adjusted for age

- AST and ALT ≤ 5 x the upper limit of normal when adjusted for age

- Serum creatinine ≤ 1.2 mg/dl; if serum creatinine is >1.2 mg/dl nuclear GFR will used
for potentially eligible participants.

- Agrees to contraception.

Exclusion criteria:

- Liver tumor involvement greater than 70% by cross sectional imaging

- Extra-hepatic visceral and osseous metastases

- Concomitant therapy for tumor (except for somatostatin analogs or bisphosphonates)

- Previous PRRT or other liver directed therapy within 12 months of consent

- Women who are pregnant, breast feeding or breast pumping.

- Another concurrent malignancy on active therapy

- Previous external-beam radiation therapy to a kidney (including scatter dose)

- Therapeutic investigational drug within 4 weeks of therapy.

- Subjects for whom, in the opinion of their physician, a 24-hour discontinuation of
somatostatin analogue therapy represents a health risk.

- Sandostatin LAR injection within 4 weeks or lanreotide injection within 8 weeks of
proposed therapy.

- Inability to lie down supine for study procedure.

- Reaction to IV contrast used for the angiogram.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring hospitalization, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that
would limit compliance with study requirements