Neuroendocrine Neoplasia's (NENs)Early Phase 1Beta plusNCT05359146
Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)
A Early Phase 1 study testing 161Tb-DOTA-LM3 and 177Lu-DOTATOC in people with Neuroendocrine Neoplasia's (NENs) and Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Neoplasia's (NENs), Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)
- What is being tested?
- 161Tb-DOTA-LM3 and 177Lu-DOTATOC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteSwitzerland
- Study dates
- 28 Mar 2023to Dec 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 11Show fewer
- 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:
- 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
Who cannot join
- 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
- Any extensive radiotherapy involving bone marrow over the last 3 months before inclusion to the study
Show all 9Show fewer
- Chemotherapy in the last 4 weeks before inclusion
- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Division of Nuclear Medicine, University Hospital Basel
Basel, 4031
Julia Fricke, Dr. med., +41 61 328 7688, julia.fricke@usb.ch
Julia Fricke, Dr. med.
About this study
Official title: Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3): Beta Plus Study
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.
Read the detailed description
Neuroendocrine neoplasia's (NENs) are a group of neoplasms arising from neuroendocrine cells and are most commonly found in the intestine, pancreas and lung. The overexpression of somatostatin receptor subtype 2 (SST2), is a characteristic of NENs and presents an important molecular target for the management of these tumours. Peptide receptor radionuclide therapy (PRRT) targets the SST2 through the administration of radiolabelled SST2 agonists such as 177Lu-DOTATOC and 177Lu-DOTATATE (Lutathera®). Although PRRT is one of the most efficient treatments for the management of NENs, it does only stabilize but not cure the disease. There is a need to improve PRRT with more effective radiopharmaceuticals. There is evidence that terbium-161 (161Tb) is more powerful that 177Lu not only in combination with SST2 agonists but particularly with SST2 antagonists.
The efficacy of PRRT can be enhanced by using a potent SST2 antagonist (DOTA-LM3) labelled with 161Tb. 161Tb-DOTA-LM3 has the following advantages compared to 177Lu-DOTATOC and 177Lu-DOTATATE: 1) SST2 antagonists bind to many more SST2-binding sites and accumulate mainly on the cellular membrane. 2) The Auger electrons of 161Tb deposit their high energy over a short distance (1-1000 nm) resulting in a high relative biological effectiveness mainly to the cell membrane which seems to be more radiosensitive than the cytoplasm. 161Tb-DOTA-LM3 does, therefore, not only deliver dose by β- radiation, but also through the emission of conversion and Auger electrons which leads to a 3 - 4 fold increased dose to single cancer cells compared to 177Lu-DOTA-LM3.
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.
- Being tested
- 161Tb-DOTA-LM3, 177Lu-DOTATOC
- 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
- Medical subject headings
- Gastro-enteropancreatic neuroendocrine tumor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
161Tb-DOTA-LM3Drug
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.
177Lu-DOTATOCDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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 Receives: 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 Receives: Drug: 161Tb-DOTA-LM3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: ~ 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.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Secondary outcomes (5)
Change in median tumour dose per gigabequerel (GBq) injected activity
Assessment of the median tumour dose per GBq injected activity (Median of the mean of 2 - 6 tumours per patient which can be identified with both compounds.). Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at ~ 3, ~ 24, ~ 72 and ~ 168 hours.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median tumour-to-bone marrow- dose ratio
Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at ~ 3, ~ 24, ~ 72 and ~ 168 hours.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median tumour-to-kidney- dose ratio
Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at ~ 3, ~ 24, ~ 72 and ~ 168 hours.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Assessment of bone marrow toxicity after test injection of 177Lu-DOTATOC and 161Tb-DOTA-LM3 using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median dose per GBq injected activity in other organs than bone marrow and kidneys
Assessment of the median dose per GBq injected activity in other organs than bone marrow and kidneys. Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at ~ 3, ~ 24, ~ 72 and ~ 168 hours.
Measured: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2022
- Study start28 Mar 2023
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neuroendocrine Neoplasia's (NENs)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation, Paul Scherrer Institute (PSI)
- Responsible party
- Sponsor
- Investigators
- Damian Wild, Prof. Dr. med., Study director, Division of Nuclear Medicine, University Hospital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05359146
- Sponsor's protocol ID
- 2022-00162; th21Wild
- Acronym
- Beta plus
- Status last verified
- Apr 2024
- First submitted
- 27 Apr 2022
- Last updated
- 19 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3): Beta Plus Study
- ClinicalTrials.gov ID
- NCT05359146
- Acronym / sponsor ID
- Beta plus / 2022-00162; th21Wild
- 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
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation, Paul Scherrer Institute (PSI)
- Study start
- 28 Mar 2023 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 3 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Neuroendocrine neoplasia's (NENs) are a group of neoplasms arising from neuroendocrine cells and are most commonly found in the intestine, pancreas and lung. The overexpression of somatostatin receptor subtype 2 (SST2), is a characteristic of NENs and presents an important molecular target for the management of these tumours. Peptide receptor radionuclide therapy (PRRT) targets the SST2 through the administration of radiolabelled SST2 agonists such as 177Lu-DOTATOC and 177Lu-DOTATATE (Lutathera®). Although PRRT is one of the most efficient treatments for the management of NENs, it does only stabilize but not cure the disease. There is a need to improve PRRT with more effective radiopharmaceuticals. There is evidence that terbium-161 (161Tb) is more powerful that 177Lu not only in combination with SST2 agonists but particularly with SST2 antagonists.
The efficacy of PRRT can be enhanced by using a potent SST2 antagonist (DOTA-LM3) labelled with 161Tb. 161Tb-DOTA-LM3 has the following advantages compared to 177Lu-DOTATOC and 177Lu-DOTATATE: 1) SST2 antagonists bind to many more SST2-binding sites and accumulate mainly on the cellular membrane. 2) The Auger electrons of 161Tb deposit their high energy over a short distance (1-1000 nm) resulting in a high relative biological effectiveness mainly to the cell membrane which seems to be more radiosensitive than the cytoplasm. 161Tb-DOTA-LM3 does, therefore, not only deliver dose by β- radiation, but also through the emission of conversion and Auger electrons which leads to a 3 - 4 fold increased dose to single cancer cells compared to 177Lu-DOTA-LM3.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Phase 0a, Group 1 | Experimental | Drug: 161Tb-DOTA-LM3, Drug: 177Lu-DOTATOCThe 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. |
| Phase 0a, Group 2 | Experimental | Drug: 161Tb-DOTA-LM3, Drug: 177Lu-DOTATOCThe 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. |
| Phase 0b, Group 1 | Experimental | Drug: 161Tb-DOTA-LM3Both 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 |
| Phase 0b, Group 2 | Experimental | Drug: 161Tb-DOTA-LM3Start 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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)
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 161Tb-DOTA-LM3161Tb-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. | Drug | Phase 0a, Group 1, Phase 0a, Group 2, Phase 0b, Group 1, Phase 0b, Group 2 |
| 177Lu-DOTATOC177Lu-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. | Drug | Phase 0a, Group 1, Phase 0a, Group 2 |
Primary outcome
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.
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
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.
Change in kidney doses after sequential injection of a non-therapeutic test activity of 161Tb-DOTA-LM3 and 177Lu-DOTATOC in the same patients.
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
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.
5 secondary outcomes
Change in median tumour dose per gigabequerel (GBq) injected activity
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median tumour-to-bone marrow- dose ratio
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median tumour-to-kidney- dose ratio
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Bone marrow toxicity using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Change in median dose per GBq injected activity in other organs than bone marrow and kidneys
Time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Damian Wild, Prof. Dr. med. study director
Division of Nuclear Medicine, University Hospital Basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing 161Tb-DOTA-LM3 and 177Lu-DOTATOC in people with Neuroendocrine Neoplasia's (NENs) and Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Julia Fricke, Dr. med. (+41 61 328 7688, julia.fricke@usb.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: ~ 3, ~ 24, ~ 72 and ~ 168 hours post injection). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2024.