Novel Imaging Techniques for Neuroendocrine Tumors

Recruiting in Palo Alto (17 mi)

Overseen by Steve Cho, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Wisconsin, Madison

Disqualifiers: Inability to lie flat, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this research is to determine if DetectnetTM PET/CT can be used to make Lutathera therapy safer for patients with neuroendocrine cancer. Participants will: * Complete two phases involving 6 visits * Undergo additional research PET/CT, and possibly SPECT/CT scans

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the effectiveness of the drug 177Lu-Dotatate for treating neuroendocrine tumors?

Research shows that 177Lu-Dotatate is effective for treating neuroendocrine tumors, as it has been used successfully in patients with these types of tumors, particularly those that are inoperable or have spread. The drug works by targeting specific receptors on the tumor cells, delivering radiation directly to them, which helps to control the growth of the tumors.

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Is Lutetium-177-DOTATATE generally safe for humans?

Lutetium-177-DOTATATE has been used as a treatment for neuroendocrine tumors, and studies have shown it can be prepared safely in hospital settings with high pharmaceutical purity. Early studies have focused on its efficacy and toxicity, indicating it is generally safe when handled properly, with fast clearance from the body through the kidneys.

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What makes the drug 177Lu-Dotatate unique for treating neuroendocrine tumors?

177Lu-Dotatate is unique because it is a radiopeptide that specifically targets somatostatin receptors on neuroendocrine tumors, delivering radiation directly to the cancer cells. This targeted approach can be more effective and have fewer side effects compared to traditional chemotherapy, as it minimizes damage to healthy tissues.

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Eligibility Criteria

This trial is for people with neuroendocrine tumors who are candidates for a treatment called Lutathera. Participants should be able to lie flat and tolerate PET/CT or SPECT/CT scans without known incompatibilities, and must be likely to follow study procedures.

Inclusion Criteria

I am a candidate for a specific treatment targeting my neuroendocrine tumor.

Exclusion Criteria

Known incompatibility to CT, SPECT, or PET scans

Unlikely to comply with study procedures, restrictions, and requirements and judged by the investigator that the participant is not suitable for participation in the study

Unable to lie flat during or tolerate PET/CT or SPECT/CT

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 visits

Dosimetry

Participants undergo dosimetry phase involving PET/CT and possibly SPECT/CT scans

3 visits

Treatment

Participants receive Lutathera treatment with dosimetry guidance

1 visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

96 hours post-dose

Participant Groups

The study tests if DetectnetTM PET/CT can make Lutathera therapy safer. It involves two phases with six visits where participants undergo additional research PET/CT, and possibly SPECT/CT scans.

Group I: Participants treated with Lutathera Experimental Treatment 4 Interventions

177Lu-Dotatate is already approved in European Union, United States for the following indications:

🇪🇺 Approved in European Union as Lutathera for:

• Unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in adults

🇺🇸 Approved in United States as Lutathera for:

• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults
• Somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in children aged 12 years and older

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of Wisconsin - Madison Madison, WI

Who Is Running the Clinical Trial?

University of Wisconsin, Madison Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

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.

2. United States pubmed.ncbi.nlm.nih.gov

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.

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT. [2019] Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has become an established procedure for the treatment of patients suffering from inoperable neuroendocrine cancers over-expressing somatostatin receptors. Success of PRRT depends on the availability of the radiolabeled peptide with adequately high specific activity, so that required therapeutic efficacy can be achieved without saturating the limited number of receptors available on the target lesions. Specific activity of the radionuclide and the radiolabeled somatostatin analog are therefore an important parameters. Although these analogs have been investigated and improved, and successfully applied for PRRT for more than 15 years, there are still many possibilities for further improvements that fully exploit PRRT with 177Lu-DOTA-TATE. The here summarized data presented herein on increased knowledge of the components of 177Lu-DOTA-TATE (especially the purity of 177Lu and specific activity of 177Lu) and the reaction kinetics during labeling 177Lu-DOTA-TATE clearly show that the peptide dose and dose in GBq can be varied. Here we present an overview of the development, formulation and optimisation of 177Lu-DOTA-TATE, mainly addressing radiochemical parameters.

4. Germany pubmed.ncbi.nlm.nih.gov

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.

5. Netherlands pubmed.ncbi.nlm.nih.gov

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.

6. England pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. [2019] The clinical applications of radiolabeled somatostatin analogue (177) Lu-DOTA-Tyr(3) -Thr(8) -Octreotide ((177) Lu-DOTATATE) constitute a promising treatment option for patients with disseminated and inoperable neuroendocrine (NET) tumors. Formulation of (177) Lu-DOTATATE in hospital radiopharmacy under aseptic conditions in a safe and reliable manner is a major constraint for its extensive use. The present work was intended to develop a kit for the safe preparation of the therapeutic radiopharmaceutical, viz. (177) Lu-DOTATATE of high quality that can be easily adapted at conventional hospital radiopharmacies. Single vial kits of DOTATATE were formulated and evaluated for suitability for radiolabeling as well as stability on its storage. Patient dose of (177) Lu-DOTATATE (7.4 GBq) could be successfully prepared using semi-automated in-house setup that assures safe handling and high yields of product of pharmaceutical purity suitable for clinical use. Fast clearance of activity via renal route was observed in preclinical biodistribution studies of (177) Lu-DOTATATE carried out in normal Swiss mice. Deployment of in-house produced (177) LuCl3 , cold kits and easy adaptability of synthesis setup at hospital radiopharmacy for preparation is likely to expand applications of peptide receptor radionuclide therapy.

7. Iran pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. [2023] Label="OBJECTIVES" NlmCategory="OBJECTIVE">Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo.

8. United States pubmed.ncbi.nlm.nih.gov

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients. [2022] Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head basis the performance of (64)Cu-DOTATATE and (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide ((111)In-DTPA-OC) as a basis for implementing (64)Cu-DOTATATE as a routine.