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

Early Phase 1
Terminated
Conditions
Neuroendocrine Tumors
Interventions
Drug: [90]Y-DOTATOC
Registration Number
NCT03724409
Lead Sponsor
Sandeep Laroia
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
3
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
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort 1[90]Y-DOTATOCSubject will be administered 2.96 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Cohort 2[90]Y-DOTATOCSubject will be administered 3.33 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Cohort 3[90]Y-DOTATOCSubject will be administered 3.7 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Cohort 4[90]Y-DOTATOCSubject will be administered 4.17 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Cohort 5[90]Y-DOTATOCSubject will be administered 4.44 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Cohort 6[90]Y-DOTATOCSubject will be administered 5.18 gigabecquerels of \[90\]Y-DOTATOC intra-aterially to the liver
Primary Outcome Measures
NameTimeMethod
Change in absolute neutrophil countThrough 6 weeks after treatment

Evaluate bone marrow toxicity using using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for absolute neutrophil count

Change in liver enzymesThrough 6 weeks after treatment

Evaluate liver toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for liver enzymes

Change in platelet countsThrough 6 weeks after treatment

Evaluate bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) severity scale for platelet count

Secondary Outcome Measures
NameTimeMethod
90Y-DOTATOC distribution48h post-infusion

Determine the distribution of 90Y-DOTATOC using post-treatment imaging

Trial Locations

Locations (1)

The Holden Comprehensive Cancer Center

🇺🇸

Iowa City, Iowa, United States

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