Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)

NCT05359146 | Recruiting Early Phase 1 DMC

• 1 other identifier: 2022-00162; th21Wild
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this phase 0 proof-of concept study is to measure the therapeutic index (tumour to dose-limiting-organ dose ratios) of 161Tb-DOTA-LM3 in comparison to the current standard 177Lu-DOTATOC in the same gastroenteropancreatic neuroendocrine tumour (GEP-NET) patients in a randomized, cross-over design, in all patients. Population to be studied are patients with diagnosed and metastasized secreting and non-secreting GEP-NEN (grade 1 and 2). The number of participants will be limited to 4 - 8 patients (phase 0a) and 4 - 8 patients (phase 0b). All patients will get the same treatment in a balanced cross-over order. The study will be divided into a phase 0a and phase 0b. Beforehand the selected patients will be randomised into two groups. In phase 0a one test injection with 161Tb-DOTA-LM3 and 177Lu-DOTATOC will administered in both randomised groups in a different order followed by \~ 3 cycles PRRT with 177Lu-DOTATOC in both groups. In phase 0b two test injections with 161Tb-DOTA-LM3 (with different peptide amounts) will administered in both randomised groups in a different order followed by \~2 cycles PRRT with 161Tb-DOTA-LM3 in both groups.

Conditions

Neuroendocrine Neoplasia's (NENs); Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)

Keywords

Somatostatin receptor subtype 2 (SST2); 161Tb-DOTA-LM3; Somatostatin receptor subtype 2 (SST2) antagonist; Peptide receptor radionuclide therapy (PRRT); 177Lu-DOTATOC (177Lu-edotreotide); Auger electrons

Outcome Measures

Primary Outcomes (2)

• Change in bone marrow doses after sequential injection of a non-therapeutic test activity of 161Tb-DOTA-LM3 and 177Lu-DOTATOC in the same patients.

  Assessment and comparison of the tumour-to-bone marrow dose ratio of 161Tb-DOTA-LM3 vs 177Lu-DOTATOC. In order to get kinetic information of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of abdomen are performed at different time points post injection 161Tb-DOTA-LM3 or 177Lu-DOTATOC: \~ 3, \~ 24, \~ 72 and \~ 168 hours.

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

• Change in kidney doses after sequential injection of a non-therapeutic test activity of 161Tb-DOTA-LM3 and 177Lu-DOTATOC in the same patients.

  Assessment and comparison of the tumour-to-kidney dose ratio of 161Tb-DOTA-LM3 vs 177Lu-DOTATOC. In order to get kinetic information of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of abdomen are performed at different time points post injection 161Tb-DOTA-LM3 or 177Lu-DOTATOC: \~ 3, \~ 24, \~ 72 and \~ 168 hours.

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

Secondary Outcomes (5)

• Change in median tumour dose per gigabequerel (GBq) injected activity

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

• Change in median tumour-to-bone marrow- dose ratio

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

• Change in median tumour-to-kidney- dose ratio

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

• Bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

• Change in median dose per GBq injected activity in other organs than bone marrow and kidneys

  ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection

Study Arms (4)

Phase 0a, Group 1

EXPERIMENTAL

The first test injection will be with 161Tb-DOTA-LM3; the second one will be with 177Lu-DOTATOC. The \~ 3 therapy cycles will be performed with 177Lu-DOTATOC. Test injection 1: 0.5 - 1 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Test injection 2 (Cross over): 0.5 - 1 GBq \~ 200 μg 177Lu-DOTATOC with renal protection Not more than 6 weeks later patients will receive \~ 3 treatment cycles with 5.6 - 7.4 GBq 177Lu-DOTATOC in an interval of about 8 weeks (clinically established amount of activity). This is standard of care and not part of the study.

Drug: 161Tb-DOTA-LM3; Drug: 177Lu-DOTATOC

Phase 0a, Group 2

EXPERIMENTAL

The first test injection will be with 177Lu-DOTATOC; the second one will be with 161Tb-DOTA-LM3. The \~ 3 therapy cycles will be performed with 177Lu-DOTATOC. Test injection 1: Group 2: 0.5 - 1 GBq \~ 200 μg 177Lu-DOTATOC with renal protection Test injection 2 (Cross over): 0.5 - 1 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 3 treatment cycles with 5.6 - 7.4 GBq 177Lu-DOTATOC in an interval of about 8 weeks (clinically established amount of activity). This is standard of care and not part of the study.

Drug: 161Tb-DOTA-LM3; Drug: 177Lu-DOTATOC

Phase 0b, Group 1

EXPERIMENTAL

Both test injections will be with 161Tb-DOTA-LM3 (with different peptide amounts). The \~ 2 therapy cycles will be performed with 161Tb-DOTA-LM3. Test injection 1: \~ 2 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Test injection 2: \~ 2 GBq \~ 300 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 2 cycles with \~ 3 GBq 161Tb-DOTA-LM3 in an interval of about 8 weeks if \~2 GBq is well tolerated

Drug: 161Tb-DOTA-LM3

Phase 0b, Group 2

EXPERIMENTAL

Start with the other peptide amount of 161Tb-DOTA-LM3. The \~ 2 therapy cycles will be performed with 161Tb-DOTA-LM3. Test injection 1: \~ 2 GBq \~ 300 μg 161Tb-DOTA-LM3 with renal protection Test injection 2: \~ 2 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 2 cycles with \~ 3 GBq 161Tb-DOTA-LM3 in an interval of about 8 weeks if \~2 GBq is well tolerated

Drug: 161Tb-DOTA-LM3

Interventions

161Tb-DOTA-LM3 DRUG

161Tb-DOTA-LM3 is a therapeutic medicinal product with three main components, namely (a) Terbium-161 (161Tb), a beta minus-, gamma- and Auger-/conversion electron-emitting radionuclide with a half-life of 6.96 days; (b) DOTA, a chelator that allows stable complexation of 161Tb; and (c) LM3, an antagonistic SST analogue which binds to SST2 receptors (SST2 receptor antagonist). All doses are presented as a sterile aqueous solution for i. v. infusion with renal protection.

Phase 0a, Group 1; Phase 0a, Group 2; Phase 0b, Group 1; Phase 0b, Group 2

177Lu-DOTATOC DRUG

177Lu-DOTATOC = 177Lu-edotreotide is a therapeutic medicinal product with three main components (a) Lutetium-177 (177Lu), a beta minus and gamma--emitting radionuclide with a half-life of 6.65 days; (b) DOTA, a chemical chelator that allows stable complexation of 177Lu; and (c) TOC (= \[Tyr\]3-octreotide) an agonistic somatostatin analogue which binds to SST2 and much less to SST5 receptors (SST2 receptor agonist). All doses are presented as a sterile aqueous solution for i. v. infusion with renal protection.

Phase 0a, Group 1; Phase 0a, Group 2

Eligibility Criteria

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

You may qualify if:

• Written consent
• Patients with diagnosed and metastasized secreting and non-secreting GEP-NEN (grade 1 and 2)
• Absence of a curative surgical option
• At least 2 measurable tumours based on RECIST 1.1 (minimal tumour diameter of 1 cm)
• Documentation of a positive 68Ga-DOTATOC/-TATE positron emission tomography (PET)/CT (in vivo detection of SST2 on GEP-NENs)
• Indication for PRRT
• Patient of any gender and of age older than 18
• Female patients of child-bearing age (who are not surgically sterilized or are less than 2 years in their menopause) must use a medically accepted contraceptive and must agree to use it during and till 3 months after the treatment. As acceptable contraceptive count sexual abstinence or double contraceptive methods: hormonal contraceptive (oral, transdermal, implants or injections) in combination with barrier methods (spiral, condom, diaphragm)
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Blood parameters:
• h) Leucocytes ≥ 3\*109/L i) Haemoglobin ≥ 90 g/L j) Thrombocytes ≥ 90\*109/L k) Estimated glomerular filtration rate ≥ 50 ml/min or Creatinine \< 150 μmol/l l) Albumin \> 25 g/L m) alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP): ≤ 5 times upper standard value n) Bilirubin ≤ 2 times upper standard value

You may not qualify if:

• Known intolerance against 177Lu, 161Tb, DOTA, TOC, LM3, SST analogues or against one of the components of 177Lu-DOTATOC or 161Tb-DOTA-LM3
• Bone/bone marrow metastases located in the lumbar spine if they affect the bone marrow dose estimation
• Ongoing infection at the screening visit or a serious infection in the past 4 weeks
• Administration of another investigational product in the last 60 days before Visit 1 Day 1
• Prior or planed administration of a therapeutic radio-pharmaceutical during 8 half-lives of the used radio-pharmaceutical's radionuclide, also during the ongoing study
• Pregnant or breastfeeding female patients. A pregnancy test will be performed in all women of child-bearing age.
• Any uncontrolled significant medical, psychiatric or surgical condition (active infection, unstable angina pectoris, cardiac arrhythmia, poorly controlled hypertension, poorly controlled diabetes mellitus \[HbA1c ≥ 9%\], uncontrolled congestive heart disease, etc.) or laboratory findings that might jeopardize the patient's safety or that would limit compliance with the objectives and assessments of the study. Any mental conditions which prevent the patient from understanding the type, extent and possible consequences of the study and/or an uncooperative attitude from the patient.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator
• Paul Scherrer Institute (PSI): collaborator

Study Sites (1)

Division of Nuclear Medicine, University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor

Interventions

177Lu-octreotide, DOTA(0)-Tyr(3)-

Study Officials

• Damian Wild, Prof. Dr. med.

  Division of Nuclear Medicine, University Hospital Basel

  STUDY DIRECTOR

Central Study Contacts

Julia Fricke, Dr. med.

CONTACT

+41 61 328 7688; julia.fricke@usb.ch

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A randomized, cross-over, prospective, single-centre, open label phase 0 study, comparing the dosimetry of 177Lu-DOTATOC and 161Tb-DOTA-LM3 in the same patients.

Study Record Dates

• First Submitted: April 27, 2022
• First Posted: May 3, 2022
• Study Start: March 28, 2023
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: April 19, 2024

Record last verified: 2024-04

Locations

CH (1)