Clinical Trials /

Yttrium-90 DOTA-TOC Intra-arterial (IA) Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumor

NCT03197012

Description:

This is a prospective, pilot, single center, open-label study in patients with metastatic neuroendocrine tumor. Eligible participants will undergo baseline assessments at enrollment. Study participants will receive a one-time administration of 90Y-DOTA-TOC via the hepatic artery. Participants in the correlative sub-study will receive 68Ga-DOTA-TOC concurrent with the 90Y-DOTA-TOC dose, and undergo additional imaging and assessment.

Related Conditions:
  • Neuroendocrine Tumor
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Yttrium-90 DOTA-TOC Intra-arterial (IA) Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumor
  • Official Title: Yttrium-90 DOTA-TOC Intra-arterial (IA) Peptide Receptor Radionuclide Therapy (PRRT) for Neuroendocrine Tumor

Clinical Trial IDs

  • ORG STUDY ID: CC# 17455
  • NCT ID: NCT03197012

Conditions

  • Neuroendocrine Tumor

Interventions

DrugSynonymsArms
90Y-DOTA-TOCYttrium-90 DOTATOCMain Study: 90Y-DOTA-TOC
68Ga-DOTA-TOCGallium-68 DOTATOCSub-study: 90Y and 68Ga-DOTA-TOC

Purpose

This is a prospective, pilot, single center, open-label study in patients with metastatic neuroendocrine tumor. Eligible participants will undergo baseline assessments at enrollment. Study participants will receive a one-time administration of 90Y-DOTA-TOC via the hepatic artery. Participants in the correlative sub-study will receive 68Ga-DOTA-TOC concurrent with the 90Y-DOTA-TOC dose, and undergo additional imaging and assessment.

Detailed Description

      Prior to the procedure, the patient will be instructed to fast overnight. Upon arrival to
      the hospital intravenous (IV) access will be placed, and Additionally, a scopolamine patch
      may be placed the night prior to treatment. Additionally a Foley catheter will be placed.

      Starting 30 minutes prior to the administration of 90Y-DOTA-TOC, an amino acid solution will
      be administered via IV. An angiographic catheter will be directed under fluoroscopic
      guidance to the appropriate location in the hepatic artery.

      The 90Y-DOTA-TOC dose will be administered over thirty minutes via the hepatic arterial
      catheter in an outpatient setting.

      Ten patients also enrolled in the correlative sub-study will receive 68Ga-DOTA-TOC
      concurrent with the therapeutic dose and 90 minutes after treatment, these patients will be
      imaged 90 minutes after treatment using a PET/CT and the following day using PET/MRI.

      All study participants will be followed up on protocol for six months for evaluation of
      toxicity and response to treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Main Study: 90Y-DOTA-TOCExperimental90Y-DOTA-TOC will be administered one time over thirty minutes via the hepatic arterial catheter in the outpatient setting. The injected dose will be 85 to 115 mCi.
  • 90Y-DOTA-TOC
Sub-study: 90Y and 68Ga-DOTA-TOCExperimental90Y-DOTA-TOC will be administered one time over thirty minutes via the hepatic arterial catheter in the outpatient setting. The injected dose will be 85 to 115 mCi. Patients enrolled in the correlative sub-study will also receive 111-259 MBq (3-7 mCi) of 68Ga-DOTA-TOC concurrent with 90Y-DOTA-TOC
  • 90Y-DOTA-TOC
  • 68Ga-DOTA-TOC

Eligibility Criteria

        Inclusion Criteria:

        1. Biopsy proven neuroendocrine tumor, which is somatostatin receptor positive as
        demonstrated on somatostatin receptor PET.

          1. All sites or origin are eligible.

          2. Functional and nonfunctional tumors are allowed. 2. Hepatic metastases on imaging
             meeting the following criteria:

        a. Liver-only or liver-dominant metastases, defined as: i. At least 10% liver parenchyma
        replacement by tumor, but less than 70% replacement of the hepatic parenchyma by tumor.

        1. For the imaging sub-study: at least one liver lesion must measure greater than 2 cm in
        size 2. For the imaging sub-study: treatment must only be performed using a single dose,
        and so arterial variant anatomy that would result in a split treatment will not be allowed
        ii. And, progression of the liver metastases demonstrated within the past twelve months
        defined as either:

          1. Appearance of any new liver lesion or

          2. 20% increase in size of at least one liver lesion. iii. Presence of low-volume
             extrahepatic lesions (including primary tumor) is allowed if they are stable and
             asymptomatic.

             b. SUVmax on 68Ga-DOTA-TOC PET of the liver metastases two times greater than the
             adjacent liver parenchyma.

          3. Not a candidate for surgical debulking.

          4. ECOG performance status 0, 1 or 2

          5. Age > 18.

          6. Ability to understand a written informed consent document, and the willingness to
             sign it.

        Exclusion Criteria:

          1. Patients not capable of getting PET study due to weight, claustrophobia, or inability
             to lie still for the duration of the exam.

             a. For patients in the imaging correlate sub-study: contraindication for undergoing
             MRI based on UCSF Radiology guidelines.

          2. Contraindication to hepatic arteriography (e.g. hepatic artery dissection and/or
             thrombosis, uncorrectable coagulopathy, severe allergy to iodinated contrast, severe
             vascular disease precluding safe hepatic artery catheterization).

          3. Any patient receiving treatment with short-acting octreotide, which cannot be
             interrupted for 48 hours before and 24 hours after the administration of
             90Y-DOTA-TOC, or any patient receiving treatment with octreotide LAR or lanreotide,
             which cannot be interrupted for at least 4 weeks before the administration of
             90Y-DOTA-TOC.

             a. Concurrent somatostatin receptor analog (SSA) allowed if progression has been
             documented and the SSA dose has been stable for at least two months. Long-acting SSA
             cannot be given within four weeks of treatment and short-acting SSA cannot be given
             with 48 hours of treatment. SSA therapy can restart one day after treatment.

          4. Interferon, everolimus (mTOR-inhibitors), sunitinib or other systemic therapies
             within 4 weeks prior to enrollment. Bevacizumab within 6 weeks prior to enrollment.

          5. Any liver directed treatment (surgery, radioembolization, chemoembolization,
             chemotherapy and radiofrequency ablation) within 12 weeks prior to enrollment.

          6. Any external beam radiation treatment for hepatic disease. Prior external beam
             radiation therapy to more than 25% of the bone marrow.

             a. Prior systemic PRRT treatment is allowed, if it was performed at least six months
             prior.

          7. Pregnancy or lactation. Women of childbearing potential and men must agree to use
             adequate contraception prior to study entry and for the duration of study
             participation

          8. Impaired liver function

               1. AST (SGOT) / ALT (SGPT) > 3 x ULN.

               2. Total bilirubin >1.5 x ULN

               3. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range.

               4. Thrombosis of the main portal vein

               5. Clinical evidence of ascites (trace ascites on imaging acceptable).

          9. Impaired bone marrow reserve

               1. Hb concentration < 8.0 g/dL;

               2. Total WBC <2x109/L (2000/mm3);

               3. Platelets <75x109/L (75x103/mm3).

         10. Creatinine clearance <50 mL/min calculated by the Cockroft Gault method.

         11. Known intracranial metastases.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR)
Time Frame:Over the duration of the study, which is estimated to be approximately 36 months
Safety Issue:
Description:Based on change in size of hepatic lesions three and six months after treatment with IA 90Y-DOTA-TOC using RECIST criteria.

Secondary Outcome Measures

Measure:Change in SUVmax between pre-treatment IV 68Ga-DOTA-TOC PET and treatment IA 68Ga-DOTA-TOC.
Time Frame:Over the duration of the study, which is estimated to be approximately 36 months
Safety Issue:
Description:Data from patients in the imaging correlate sub-study only
Measure:Correlation between uptake on IA 68Ga-DOTA-TOC PET/CT compared to 24-hour post-treatment IA 90Y-DOTA-TOC PET/MRI.
Time Frame:Over the duration of the study, which is estimated to be approximately 36 months
Safety Issue:
Description:Data from patients in the imaging correlate sub-study only

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Thomas Hope

Trial Keywords

  • neuroendocrine tumor (NET)
  • Peptide Receptor Radionuclide Therapy (PRRT)
  • somatostatin receptor (SSTR)

Last Updated

June 21, 2017