Clinical trial NCT03724409: Selective Intra-arterial Injection of PRRT in Neuroendocrine Tumor Patients With Liver Metastases
Official title: Selective Intra-arterial Injection of Peptide Receptor Radionuclide Therapy (PRRT) in Neuroendocrine Tumor Patients With Liver Metastases
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Neuroendocrine Tumors
Keywords: PRRT
Radionuclide
DOTATOC
intra-arterial
peptide receptor radiotherapy
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Holden Comprehensive Cancer Center
name: National Cancer Institute (NCI)
First posted: 2018-10-30
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This is a sequential early phase 1 study using Storer's phase 1 design B.
Primary purpose: TREATMENT

Brief summary: This is a safety study to determine the phase 1 starting dose of \[90\]Yttrium-DOTATOC when it is administered intravenously for patients with neuroendocrine tumors that have spread to the liver.

Detailed description: \[90\]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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in liver enzymes
timeFrame: Through 6 weeks after treatment
measure: Change in platelet counts
timeFrame: Through 6 weeks after treatment
measure: Change in absolute neutrophil count
timeFrame: Through 6 weeks after treatment
Secondary outcomes:
measure: 90Y-DOTATOC distribution
timeFrame: 48h post-infusion
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: The Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: University of Iowa
name: M. S O'Dorisio, MD, PhD
role: STUDY_CHAIR
affiliation: University of Iowa
name: Sandeep Laroia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kennedy A, Bester L, Salem R, Sharma RA, Parks RW, Ruszniewski P; NET-Liver-Metastases Consensus Conference. Role of hepatic intra-arterial therapies in metastatic neuroendocrine tumours (NET): guidelines from the NET-Liver-Metastases Consensus Conference. HPB (Oxford). 2015 Jan;17(1):29-37. doi: 10.1111/hpb.12326. Epub 2014 Sep 4.