University Hospital, Basel, Switzerland
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.
Neuroendocrine Neoplasia's (NENs)
Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)
161Tb-DOTA-LM3
177Lu-DOTATOC
Early Phase 1
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 Type : | Interventional |
Estimated Enrollment : | 16 participants |
Masking: | None (Open Label) |
Primary Purpose: | Basic Science |
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 |
Actual Study Start Date : | March 28, 2023 |
Estimated Primary Completion Date : | December 2025 |
Estimated Study Completion Date : | December 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: Phase 0a, Group 1 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 |
Experimental: Phase 0a, Group 2 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: 177Lu-DOTATOC |
Experimental: Phase 0b, Group 1 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 |
Experimental: Phase 0b, Group 2 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: 177Lu-DOTATOC |
Ages Eligible for Study: | 18 Years |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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Recruiting
Division of Nuclear Medicine, University Hospital Basel
Basel, Switzerland, 4031