Lutetium-177 Therapy for Neuroendocrine Tumors
(LUMOD-ID Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Iowa
Disqualifiers: Pregnancy, Active infection, Heart failure, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?The goal of this study is to learn if individualized dosimetry-based prescribing of Lutetium-177 DOTATATE (Lutathera, Novartis Pharmaceuticals) improves treatment outcomes for adults with unresectable neuroendocrine tumors. To investigate this, study participants will:
* Undergo Somatostatin Receptor (SSTR) positron emission tomography (PET) imaging, such as a DOTATOC PET/CT scan
* Be randomized to receive standard treatment (as per FDA guidelines) or investigational treatment (customized dosing of Lutathera based upon dosimetry)
* Undergo blood tests for 4 to 8 weeks after each Lutathera treatment
* Complete patient reported outcome questionnaires
* Visit the clinic for follow-up about every 8 weeks.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, a review of your current medications will be conducted to confirm the appropriateness of Lutathera treatment.
What data supports the effectiveness of the treatment Lutetium-177 Therapy for Neuroendocrine Tumors?
Research shows that Lutetium-177 DOTATATE is effective in treating neuroendocrine tumors, with patients experiencing tumor shrinkage and improved quality of life. The treatment has a median progression-free survival of over 40 months and can be safely administered with minimal side effects, especially when kidney-protective agents are used.
12345Is Lutetium-177 therapy safe for humans?
Lutetium-177 therapy has been shown to be generally safe for humans, but it can have side effects, including potential toxicity to the kidneys, liver, and blood cells, and there is a risk of developing a second cancer. It is important for patients to discuss these risks with their healthcare provider.
12367What makes Lutetium-177 therapy unique for treating neuroendocrine tumors?
Lutetium-177 therapy is unique because it uses a radioactive substance to target and bind to specific receptors on neuroendocrine tumor cells, delivering radiation directly to the tumor and minimizing damage to surrounding healthy tissue. This targeted approach is different from traditional chemotherapy, which affects both cancerous and healthy cells.
12348Eligibility Criteria
This trial is for adults with neuroendocrine tumors that can't be removed by surgery. Participants will need to undergo special PET imaging scans and are willing to follow up regularly at the clinic. Specific eligibility details aren't provided, but typically include factors like age, health status, and type of tumor.Inclusion Criteria
Platelet count within normal limits within 28 days of treatment day 1
Stated willingness to comply with all study procedures and availability for the duration of the study
Neutrophil count within normal limits within 28 days of treatment day 1
+10 more
Exclusion Criteria
Individuals who are pregnant or lactating
I have previously undergone peptide-receptor radiotherapy.
I do not have any serious illnesses or social situations that would stop me from following the study's requirements.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive Lutetium-177 DOTATATE treatment every 8 weeks for up to 4 cycles, with dosimetry-based adjustments for investigational group
32 weeks
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with visits at 2, 3, 6, and 12 months post-treatment
12 months
4 visits (in-person)
Long-term follow-up
Participants have life-long follow-up to monitor for late-onset radiation side effects
Participant Groups
The study tests if customizing doses of Lutathera based on individual dosimetry leads to better outcomes compared to standard FDA-approved treatment. Patients will either receive the standard dose or a personalized dose determined by advanced imaging techniques.
2Treatment groups
Experimental Treatment
Active Control
Group I: Dosimetry-based lutetium Lu 177 dotatate therapyExperimental Treatment1 Intervention
Intravenous administration of lutetium Lu 177 dotatate once every 8 weeks for up to 4 total cycles.
Intended administered radioactivity:
Cycle 1: 200 millicuries (mCi) Cycles 2, 3, and 4: based upon dosimetry for radiation exposure to bone marrow (no more than 1 Gy per administration) and kidneys (maximum dose 28 Gy total). Not to exceed 400 millicuries (mCi) per cycle (1400 mCi maximum for all cycles).
Group II: Standard lutetium Lu 177 dotatateActive Control1 Intervention
Intravenous administration of lutetium Lu 177 dotatate once every 8 weeks for up to 4 total cycles. Each cycle is intended to receive 200 millicuries of radioactivity for a total treatment of 800 millicuries.
Lutetium Lu 177 dotatate therapy is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Lutathera for:
- Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults
🇪🇺 Approved in European Union as Lutathera for:
- Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Holden Comprehensive Cancer Center at the University of IowaIowa City, IA
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Who Is Running the Clinical Trial?
University of IowaLead Sponsor
NovartisIndustry Sponsor
References
Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. [2019]Lutetium-177 DOTA-D-Phe1-Tyr3-octreotide (Lu-DOTATATE) is a treatment option for patients with well-differentiated metastatic neuroendocrine tumours. Our centre started administering this therapy in 2012. The aim of this study was therefore to analyse the first cohort of patients treated with Lu-DOTATATE to determine its early efficacy and toxicity.
The development and validation of a high performance liquid chromatography method to determine the radiochemical purity of [177Lu]Lu-HA-DOTA-TATE in pharmaceutical preparations. [2021]Lutetium-177 [177Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([177Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [177Lu]LuCl3 cannot exceed 2% of the radioactive dose. Since no monograph is available for [177Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [177Lu]LuCl3 and [177Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [177Lu]LuCl3 were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [177Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [177Lu]Lu-HA-DOTA-TATE.
Comparison of [(177)Lu-DOTA(0),Tyr(3)]octreotate and [(177)Lu-DOTA(0),Tyr(3)]octreotide: which peptide is preferable for PRRT? [2019]Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC) and [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE), to see which peptide should be preferred for PRRT with (177)Lu.
Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. [2022]Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs.
Lutetium-labelled peptides for therapy of neuroendocrine tumours. [2022]Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with (177)Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with (177)Lu-[DOTA(0),Tyr(3)]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with (177)Lu-DOTATATE as well as the limited side effects with additional cycles of (177)Lu-DOTATATE suggest that more cycles of (177)Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of (90)Y-[DOTA(0),Tyr(3)]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with (177)Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with (177)Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours.
Lutetium Lu-177 Dotatate Flare Reaction. [2022]Lutetium Lu-177 dotatate is the first peptide receptor radionuclide therapy approved by the US Food and Drug Administration. Well-designed studies in Europe have shown dramatic effectiveness in improving progression-free survival in patients with gastroenteropancreatic neuroendocrine tumors, which are progressive and generally metastatic. This therapy is a molecular targeted therapy linking a beta-emitting radioisotope to dotatate, which binds tightly to somatostatin receptors on neuroendocrine tumors cells. Various adverse effects of this therapy have been reported in the literature, including potential toxicity to renal, hepatic, and hematologic tissues and risk of second malignancy. Our study sought to explore acute adverse effects in this patient population.
Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">The use of lutetium-177 (177Lu)-based radiopharmaceuticals in peptide receptor nuclear therapy is increasing, but so is the number of nuclear medicine workers exposed to higher levels of radiation. In recent years, [177Lu]Lu-DOTA-TATE has begun to be widely used for the treatment of neuroendocrine tumours. However, there are few studies evaluating the occupational radiation exposure during its administration, and there are still some challenges that can result in higher doses to the staff, such as a lack of trained personnel or fully standardised procedures. In response, this study aims to provide a comprehensive analysis of occupational doses to the staff involved in the administration of [177Lu]Lu-DOTA-TATE.
Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. [2013]Therapy using the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate (177Lu-octreotate) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) has been used primarily in gastroenteropancreatic neuroendocrine tumors. Here we present the effects of this therapy in a small number of patients with metastasized or inoperable paragangliomas, meningiomas, small cell lung carcinomas (SCLCs), and melanomas.