Impact of Peptides and Chelators on Somatostatin Receptor Antagonists

A Prospective Study to Evaluate the Impact of Different Peptides and Chelators on the Diagnostic Performance of PET/CT Using Gallium-68 Labeled Somatostatin Receptor Antagonists

Somatostatin receptor antagonists are emerging agents in molecular imaging of neuroendocrine tumors. There're two main antagonist peptides, namely JR11 and LM3, which can be coupled with different chelators, DOTA and NODAGA. Previous studies by our and other groups have revealed the different diagnostic performances of these tracers. However, head-to-head comparison data is still missing. In this study, we aim to evaluate the diagnostic performance of four different antagonists, that is, NODAGA-LM3, DOTA-LM3, and NODAGA-JR11, all labeled with gallium-68.

Study Overview

• Status: Unknown
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Diagnostic test: 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 PET/CT; Diagnostic test: 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 PET/CT

Detailed Description

Patients will be randomly assigned into two arms:

Arm A : 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 Arm B : 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11

In each arm, patients will undergo PET/CT using assigned tracers. Lesion detection, lesion SUV, and the tumor-to-background ratio will be compared.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Yupei Zhao, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent.
• Patients of either gender, aged ≥ 18 years.
• Histologically confirmed diagnosis of well-differentiated neuroendocrine tumor.
• A diagnostic computed tomography (CT) or magnetic resonance imaging (MRI) of the tumor region within the previous 6 months prior to dosing day is available.
• At least 1 measurable lesion based on RECIST v1.1.
• Blood test results as follows (White blood cell: ≥ 3*10^9/L, Hemoglobin: ≥ 8.0 g/dL, Platelets: ≥ 50x10^9/L, Alanine aminotransferase / Aspartate aminotransferase / Alkaline phosphatase: ≤ 5 times the upper limit of normal (ULN), Bilirubin: ≤ 3 times ULN)
• Serum creatinine: within normal limits or < 120 μmol/L for patients aged 60 years or older.
• Calculated Glomerular filtration rate (GFR) ≥ 45 mL/min.

Exclusion Criteria:

• Known hypersensitivity to Gallium-68, to NODAGA, to DOTA, to LM3, to JR11 or to any of the excipients of Gallium-68 DOTA-LM3, Gallium-68 NODAGA-LM3, or Gallium-68 NODAGA-JR11.
• Presence of active infection at screening or history of serious infection within the previous 6 weeks.
• Therapeutic use of any somatostatin analog, including long-acting Sandostatin (within 28 days) and short-acting Sandostatin (within 2 days) prior to study imaging. If a patient is on long-acting Sandostatina, then a wash-out phase of 28 days is required before the injection of the study drug. If a patient is on short-acting Sandostatin, then a wash-out phase of 2 days is required before the injection of the study drug.
• Any neuroendocrine tumor-specific treatment between scans.
• Proofs of negative somatostatin receptor expression by previous scans or Immunohistochemical staining results.
• Prior or planned administration of a radiopharmaceutical within 8 half-lives of the radionuclide used on such radiopharmaceutical including at any time during the current study.
• Pregnant or breast-feeding women.
• Current history of any malignancy other than neuroendocrine tumor; patients with a secondary tumor in remission of > 5 years can be included.
• Any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and/or evidence of an uncooperative attitude.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LM3 group; In this arm, patients will undergo PET/CT using 68Ga-NODAGA-LM3 (40ug peptide/150-200MBq) and 68Ga-DOTA-LM3 (40ug peptide/150-200MBq) on two consecutive days. The scan will be acquired at 1hour post-injection.	Diagnostic test: 68Ga-NODAGA-LM3 and 68Ga-DOTA-LM3 PET/CT; Patients will undergo PET/CT using 68Ga-NODAGA-LM3 (40ug peptide/150-200MBq) and 68Ga-DOTA-LM3 (40ug peptide/150-200MBq) on two consecutive days. The scan will be acquired at 1hour post-injection.
Experimental: NODAGA group; In this arm, patients will undergo PET/CT using 68Ga-NODAGA-LM3 (40ug peptide/150-200MBq) and 68Ga-NODAGA-JR11 (40ug peptide/150-200MBq) on two consecutive days. The scan will be acquired at 1hour post-injection.	Diagnostic test: 68Ga-NODAGA-LM3 and 68Ga-NODAGA-JR11 PET/CT; Patients will undergo PET/CT using 68Ga-NODAGA-LM3 (40ug peptide/150-200MBq) and 68Ga-NODAGA-JR11 (40ug peptide/150-200MBq) on two consecutive days. The scan will be acquired at 1hour post-injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lesion numbers	Determination of lesion numbers of 68Ga-NODAGA-LM3, 68Ga-DOTA-LM3, and 68Ga-NODAGA-JR11 scan.	At 1-hours post-injection
Standard uptake value (SUV)	Determination of SUV for detected lesions and discernible organs of 68Ga-NODAGA-LM3, 68Ga-DOTA-LM3, and 68Ga-NODAGA-JR11 scan.	At 1-hours post-injection

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Wenjia Zhu, MD, Peking Uion Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Actual): November 5, 2020
• Last Update Submitted That Met QC Criteria: November 3, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: PET/CT; somatostatin receptor antagonist
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors
• Other Study ID Numbers: ANTANET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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