68Ga-DOTA-MGS5 PET/CT in Patients With Advanced Neuroendocrine Tumours

NCT06155994 | Completed Phase 1 DMC

• 1 other identifier: EudraCT No.: 2020-003932-26
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

68Ga-labelled \[DOTA0,DGlu1,desGlu2-6,(N-Me)Nle11,1-Nal13\]minigastrin (68Ga-DOTA-MGS5) is a novel radiopharmaceutical for intravenous administration for evaluation of the cholecystokinin receptor (CCK2R) status in patients with CCK2R-related malignancies. CCK2R is expressed at high incidence in medullary thyroid carcinomas (92%) and frequently expressed also in gastroenteropancreatic neuroendocrine tumours (GEP-NET, 22%). In this phase I/IIa study the safety of administration and the biodistribution of 68Ga-DOTA-MGS5 will be evaluated in patients with advanced MTC as well as gastroenteropancreatic and bronchopulmonary NET. In addition, the visualization of tumour lesions as well as the absorbed organ and tumour radiation dose will be evaluated. The new positron emission tomography (PET) imaging modality has the potential to improve the diagnostic accuracy in patients with advanced MTC as well as gastroenteropancreatic and bronchopulmonary NET. After successful application in diagnostic imaging, CCK2R targeting with therapeutic radionuclides bears high potential also to improve the therapeutic management of patients with advanced disease.

Conditions

Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (3)

• Clinical safety and tolerability

  The assessment of standard safety and tolerability will include physical examination, measurement of vital signes, electrocardiogram, laboratory tests (haematology, blood chemistry, coagulation parameters, semiquantitative urine analysis, pregnancy test in women of childbearing potential, tumour markers). Clinical relevant changes will be reported. Any serious adverse reactions (SAR) and any suspected unexpected serious adverse reaction (SUSAR) related to the study drug defined by the CTCAE v5.0 will be monitored. The tolerability and safety of the administration of a diagnostic dose of 68Ga-DOTA-MGS5 in patients is determined by the absence of increased number of SAR and SUSAR compared to other peptide-based radiotracers.

  day -16 to 0 before administration, day 0 to 1 after administration; day 7 to16 after administration

• Whole-body distribution and dosimetry

  Up to 6 whole-body PET/CT scans will be acquired in the first six patients. The number of scans will be reduced to 2 in the last six patients. PET/CT scans will be used for semiquantitative evaluation of tissues and organs with physiologic tracer uptake by measuring the intensity of tracer uptake with the maximum and mean standardised uptake value (SUVmax, SUVmean). From these measurements time activity curves will be generated and residence times of 68Ga-DOTA-MGS5 in normal organs and tumour lesions, as well as absorbed tumour-to-organ doses and effective whole-body dose will be calculated.

  day 0

• Assessment of pharmacokinetics

  Venous blood sampling and urine collection for pharmacokinetic assessments will be performed in the first six patients to calculate the half-life of 68Ga-DOTA-MGS5 in blood and quantify the urinary excretion.

  day 0

Secondary Outcomes (3)

• Preliminary targeting properties

  day 0

• Comparison with other standard imaging modalities

  day 0

• Description of lesion agreement

  day 0

Other Outcomes (1)

• HPLC radiochromatography of blood and urine

  day 0

Study Arms (1)

Group A and B

EXPERIMENTAL

Group A: six patients with advanced medullary thyroid carcinoma Group B: six patients with advanced gastroenteropancreatic and bronchopulmonary neuroendocrine tumours

Drug: 68Ga-DOTA-MGS5

Interventions

68Ga-DOTA-MGS5 DRUG

intravenous administration

Also known as: 68Ga-labelled minigastrin analogue

Group A and B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years, men and women
• Understanding and provision of signed and dated written informed consent by the patient or legally acceptable representative prior to any study-specific procedures
• Karnofsky performance status \>70
• Histopathologically diagnosed locally advanced or metastatic MTC with calcitonin level \>100 pg/mL after total thyroidectomy or other histologically diagnosed advanced gastroenteropancreatic and bronchopulmonary NET with known metastases
• Male subjects must-agree to use condoms throughout the study period and for 1 month after study termination if their partner is of childbearing potential and is using no contraception. They agree not to donate semen during study period and for 1 month after study termination.
• Women of childbearing potential (WOCBP) must have a negative urine/serum pregnancy test. WOCBP who are sexually active, agree to use highly-effective means of contraception during the study and for at least 6 months post-study treatment. Allowed are accepted and effective non-hormonal methods of contraception and sexual abstinence or vasectomised partners (\>3 months previously). Vasectomy has to be confirmed by two negative semen analyses.

You may not qualify if:

• Other known co-existing malignancies except patients with a history of malignant tumours in complete remission \>3 years, with no evidence of recurrence \<5 years
• Participation in any other investigational trial within 3 months of study entry
• Treatment with tyrosine kinase inhibitors within 1 month before study entry
• Organ allograft requiring immunosuppressive therapy
• Renal insufficiency with an eGFR \<30 mL/min/1.72m2
• Higher than grade 2 hematotoxicity (CTC \>2)
• Clinically abnormal ECG (signs of ischemia, high grade ventricular arrhythmia, high grade supra-ventricular arrhythmia)
• Pregnancy, breast-feeding
• Patients with concurrent illnesses or severe infectious diseases that might preclude study completion
• Patients with bladder outflow obstruction or unmanageable urinary incontinence
• Known hypersensitivity to gallium-68 or to any of the excipients of DOTA-MGS5
• Any condition that precludes raised arms position for prolonged imaging purposes
• Prior administration of a radiopharmaceutical within a period corresponding to 8 half-lives of the radionuclide used on such radiopharmaceutical
• Clinically significant illness or clinically relevant trauma within 3 weeks before the administration of the investigational product
• Persons with any kind of dependency on the investigator or employed by the sponsor or investigator

Sponsors & Collaborators

• Medical University Innsbruck: lead
• Novartis: collaborator

Study Sites (1)

Department of Nuclear Medicine, Medical University of Innsbruck

Innsbruck, 6020, Austria

Location

Related Publications (1)

• von Guggenberg E, di Santo G, Uprimny C, Bayerschmidt S, Warwitz B, Hormann AA, Zavvar TS, Rangger C, Decristoforo C, Sviridenko A, Nilica B, Santo G, Virgolini IJ. Safety, Biodistribution, and Radiation Dosimetry of the 68Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors. J Nucl Med. 2025 Feb 3;66(2):257-263. doi: 10.2967/jnumed.124.268877.

  PMID: 39819687 DERIVED

MeSH Terms

Conditions

Neuroendocrine Tumors

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Irene Virgolini, MD

  Medical University of Innsbruck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2023
• First Posted: December 5, 2023
• Study Start: January 20, 2021
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: December 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)