Treatment Using 177Lu-DOTA-EB-TATE in Patients With Advanced Neuroendocrine Tumors

Treatment of a Long-lasting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients With Advanced Metastatic Neuroendocrine Tumors

This is a prospective study to investigate the long-lasting radiolabeled somatostatin analogue based peptide receptor radionuclide therapy and evaluate response to 177Lu-DOTA-EB-TATE in patients with advanced metastatic neuroendocrine tumors. Different groups with doses of 0.37GBq-0.74GBq (10-20 mCi) and 1.85GBq (50 mCi)of 177Lu-DOTA-EB-TATE, 3.7GBq (100 mCi)of 177Lu-DOTA-TATE will be injected intravenously. Besides, we evaluated the safety and dosimetry of 3.7GBq (100 mCi) of 177Lu-DOTA-EB-TATE with and without amino acid infusion. All patients will undergo 68Ga-DOTATATE PET/CT scans before and after the treatment.

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-DOTA-EB-TATE 1; Drug: 177Lu-DOTA-EB-TATE 2; Drug: 177Lu-DOTA-EB-TATE 3; Drug: 177Lu-DOTA-TATE; Drug: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE with amino acids (lysine and arginine); Drug: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE without amino acids (lysine and arginine)

Detailed Description

Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms that can develop anywhere in the body and arise from neuroendocrine cells throughout the endocrine system. The most recent NCCN guidelines for unresectable and metastatic NET recommend somatostatin analogues as first-line treatment, but do not recommend a particular treatment sequence for the remaining therapies. Radiolabeled somatostatin analogue therapy, also known as peptide receptor radionuclide therapy has become a well-accepted treatment for patients with well to moderately differentiated unresectable or metastatic NETs and disease progression after first-line treatment. However, a major problem in the therapeutic use of 177Lu-Dotatate has been its short half-life and fast rate of clearance. Kidney is considered one of the dose-limiting organs in peptide receptor radionuclide therapy (PRRT). Amino acid has been infused to reduce renal absorbed dose by inhibiting the proximal tubular reabsorption of the radiopeptide. This study was designed to compare the efficacy of a long-lasting radiolabeled somatostatin analogue 177Lu-DOTA-EB-TATE with 177Lu-DOTA-TATE in patients with advanced metastatic neuroendocrine tumors and evaluate the safety and dosimetry of 3.7GBq (100 mCi) of 177Lu-DOTA-EB-TATE with and without amino acid infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Hao Wang, PhD.; Phone Number: +86 10 69154196

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults who had neuroendocrine tumors and had metastasized, that were with histologically confirmed, inoperable and had showed disease progression according to Response Evaluation Criteria in Solid Tumors [RECIST]. Tumors were with well-differentiated histologic features and a Ki67 index of 0 to 20%. Target tumors were selected from CT, MRI, and 68Ga-DOTA-TATE PET/CT, with confirmed somatostatin receptorexpressing and at least one lesion has higher uptake than that of normal liver parenchyma on 68Ga-DOTA-TATE PET imaging within 1 weeks.

Exclusion Criteria:

• The exclusion criteria were a serum creatinine level of more than 150 μmol per liter, baseline measured GFR of less than 50 mL/min/1.73 m2, determined by 99mTc-DTPA renal function examination, a hemoglobin level of less than 8.0 g/dl, a white-cell count of less than 2.0× 109/L, a platelet count of less than 75 × 109/L, a total bilirubin level of more than 3 times the upper limit of the normal range and a serum albumin level of more than 3.0 g per deciliter, cardiac insufficiency including carcinoid heart valve disease, a severe allergy or hypersensitivity to radiographic contrast material, claustrophobia, and pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 177Lu-DOTA-EB-TATE 1; The patients were intravenously injected with single dose 0.37GBq-0.74GBq (10-30 mCi) of 177LuDOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.	Drug: 177Lu-DOTA-EB-TATE 1; The patients were intravenously injected with single dose 0.37GBq-0.74GBq (10-30 mCi) of 177Lu-DOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.
Experimental: 177Lu-DOTA-EB-TATE 2; The patients were intravenously injected with single dose 1.85GBq (50 mCi) of 177LuDOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.	Drug: 177Lu-DOTA-EB-TATE 2; The patients were intravenously injected with single dose 1.85GBq (50 mCi) of 177Lu-DOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.
Experimental: 177Lu-DOTA-EB-TATE 3; The patients were intravenously injected with single dose 3.7 GBq (100 mCi) of 177LuDOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.	Drug: 177Lu-DOTA-EB-TATE 3; The patients were intravenously injected with single dose 3.7GBq (100 mCi) of 177Lu-DOTA-EB-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.
Experimental: 177Lu-DOTA-TATE; The patients were intravenously injected with single dose 3.7 GBq (100 mCi) of 177LuDOTA-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.	Drug: 177Lu-DOTA-TATE; The patients were intravenously injected with single dose 3.7GBq (100 mCi) of 177Lu-DOTA-TATE and underwent 68Ga-DOTATATE PET/CT scans before and after the treatment.
Experimental: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE with amino acids (lysine and arginine); The patients were intravenously injected with 3.7 GBq (100 mCi) of 177LuDOTA-TATE and amino acids (lysine and arginine).	Drug: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE with amino acids (lysine and arginine); The patients were intravenously injected with 3.7GBq (100 mCi) of 177Lu-DOTA-EB-TATE and amino acids (lysine and arginine).
Experimental: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE without amino acids (lysine and arginine); The patients were intravenously injected with 3.7 GBq (100 mCi) of 177LuDOTA-TATE without amino acids (lysine and arginine).	Drug: 3.7 GBq (100 mCi) of 177Lu-DOTA-EB-TATE without amino acids (lysine and arginine); The patients were intravenously injected with 3.7GBq (100 mCi) of 177Lu-DOTA-EB-TATE without amino acids (lysine and arginine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of standardized uptake value of 68Ga-DOTA-TATE before and after the treatment in metastatic neuroendocrine tumors	The semiquantitative analysis will be performed by the same person for all the cases, and the standardized uptake value before and after the treatment in metastatic neuroendocrine tumors will be measured.	1 year
the safety of 3.7GBq of 177Lu-DOTA-EB-TATE with and without amino acid infusion.	Hematological parameters, liver, and renal function at baseline, 1 week and 4 weeks after PRRT were tested. 99mTc-DTPA dynamic renal imaging for the determination of the glomerular filtration rate (GFR) was performed at baseline and 8 weeks after each cycle of PRRT.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the dosimetry of 3.7GBq of 177Lu-DOTA-EB-TATE with and without amino acid infusion.	the absorbed dose for kidney and whole-body evaluated through HERMES software.	1 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Liu Q, Cheng Y, Zang J, Sui H, Wang H, Jacobson O, Zhu Z, Chen X. Dose escalation of an Evans blue-modified radiolabeled somatostatin analog 177Lu-DOTA-EB-TATE in the treatment of metastatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2020 Apr;47(4):947-957. doi: 10.1007/s00259-019-04530-1. Epub 2019 Dec 12.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2017
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: March 23, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): August 31, 2022
• Last Update Submitted That Met QC Criteria: August 28, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Chelating Agents; Sequestering Agents; Lutetium Lu 177 dotatate; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; (177)Lu-DOTA-EB-TATE
• Other Study ID Numbers: PekingUMCH-NM018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No