Novel Imaging Techniques for Neuroendocrine Tumors

Overseen By Radiology Studies

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Disqualifiers: Inability to lie flat, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 visit

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a special imaging technique can make the cancer treatment Lutathera (177Lu-Dotatate) safer for patients with neuroendocrine tumors. It includes additional scans to assess the imaging's compatibility with the treatment. This trial may suit those already scheduled to receive Lutathera for tumors with specific markers (somatostatin receptors). Participants must attend several visits and undergo various scans to help researchers gather important safety data. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

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 prior data suggests that these imaging techniques are safe for patients with neuroendocrine tumors?

Research has shown that 177Lu-Dotatate, also known as Lutathera, has been tested in patients with neuroendocrine tumors. Safety data indicate it is generally well-tolerated. One study found that common side effects included nausea and diarrhea, affecting over 20% of patients. Additionally, about 44% of patients experienced low white blood cell counts, and 20% had increased levels of a liver enzyme.

While these side effects might seem serious, they can be managed. Lutathera has already received FDA approval for certain neuroendocrine tumors, suggesting it is generally safe. However, individual experiences can vary, so discussing potential risks with a healthcare provider is advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments 177Lu-Dotatate and 64Cu-Dotatate for neuroendocrine tumors because they offer a novel approach to imaging and treatment. Unlike traditional options that primarily involve surgery or chemotherapy, 177Lu-Dotatate uses a targeted radiotherapy approach, delivering radiation directly to the tumor cells via a somatostatin analog, which can improve precision and reduce harm to healthy tissue. Meanwhile, 64Cu-Dotatate is a cutting-edge imaging agent that could enhance the detection and monitoring of tumors by providing clearer and more detailed PET scans. Together, these treatments have the potential to improve both the accuracy of tumor visualization and the effectiveness of targeted therapy.

What evidence suggests that this trial's imaging techniques could be effective for neuroendocrine tumors?

Research shows that 177Lu-Dotatate, also known as Lutathera, effectively treats neuroendocrine tumors. The NETTER-1 trial found that it helps patients live longer without disease progression. Patients receiving this treatment reported an improved quality of life. Specifically, one study found that patients lived an average of 22.8 months without disease worsening with Lutathera, compared to 8.5 months with other treatments. Additionally, Lutathera has been shown to shrink or stabilize tumors more effectively than some treatments, such as everolimus. Overall, these findings suggest that 177Lu-Dotatate is a promising option for managing neuroendocrine tumors. ^{5 6 7 8 9}

Who Is on the Research Team?

Steve Cho, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 177Lu-Dotatate
• 64Cu-Dotatate
• DetectnetTM PET/CT
• SPECT/CT

Trial Overview 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.

How Is the Trial Designed?

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

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

Published Research Related to This Trial

In a study involving seven patients with neuroendocrine tumors, the peptide [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-DOTATATE) demonstrated a longer residence time in tumors compared to [(177)Lu-DOTA(0),Tyr(3)]octreotide ((177)Lu-DOTATOC), suggesting it may be more effective for peptide receptor radionuclide therapy (PRRT).

Although (177)Lu-DOTATATE resulted in longer residence times in the kidneys, the overall tumor dose was still higher, making (177)Lu-DOTATATE the preferred choice for PRRT despite potential kidney dose concerns.

NCBI (Pubmed)

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? Esser, JP., Krenning, EP., Teunissen, JJ., et al.[2019]

In a study of 79 patients with progressive neuroendocrine tumors treated with Lu-DOTATATE, 13% showed a partial response and 64% had stable disease, with a median time to progression of 28 months overall.

The treatment was found to be safe, with only a few patients experiencing mild toxicity, including grade 1 haematotoxicity and nephrotoxicity, supporting its use as an effective option for managing these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early efficacy of and toxicity from lutetium-177-DOTATATE treatment in patients with progressive metastatic NET. Pencharz, D., Walker, M., Yalchin, M., et al.[2019]

In a study involving 112 patients with neuroendocrine tumors (NETs), (64)Cu-DOTATATE demonstrated significantly better diagnostic sensitivity and accuracy (97%) compared to (111)In-DTPA-OC (87% sensitivity, 88% accuracy), indicating its superior performance in detecting NETs.

(64)Cu-DOTATATE identified more lesions than (111)In-DTPA-OC in 75% of patients, and in 36% of cases, it detected lesions in organs not identified by the older method, suggesting it could provide a more comprehensive assessment of disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

64Cu-DOTATATE PET for Neuroendocrine Tumors: A Prospective Head-to-Head Comparison with 111In-DTPA-Octreotide in 112 Patients. Pfeifer, A., Knigge, U., Binderup, T., et al.[2022]

177Lu-DOTA-Peptide 2, a new radioantagonist, showed high stability and selective binding to somatostatin receptors in HT-29 colorectal cancer cells, indicating its potential for targeted therapy.

The study demonstrated that 177Lu-DOTA-Peptide 2 has a low internalization rate and a high tumor uptake, making it a promising candidate for radionuclide therapy in treating somatostatin receptor-positive tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells. Behnammanesh, H., Erfani, M., Hajiramezanali, M., et al.[2023]

Peptide receptor radionuclide therapy (PRRT) using 177Lu-DOTA-TATE is an effective treatment for inoperable neuroendocrine cancers that over-express somatostatin receptors, relying on the specific activity of the radiolabeled peptide to ensure therapeutic efficacy without receptor saturation.

Ongoing improvements in the purity and specific activity of 177Lu, as well as the reaction kinetics during the labeling process, can enhance the effectiveness of PRRT, allowing for better dose variations and optimization of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT. Breeman, WA., Chan, HS., de Zanger, RM., et al.[2019]

The study developed and validated a high-performance liquid chromatography (HPLC) method for quality control of the radiopeptide [177Lu]Lu-DOTA-TATE, ensuring its radiochemical purity meets therapeutic standards (95-105% of label claim).

The HPLC method demonstrated accuracy, precision, and sensitivity, making it suitable for clinical samples, which is crucial for the safe and effective use of [177Lu]Lu-DOTA-TATE in treating neuroendocrine tumors.

NCBI (Pubmed)

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. van Andel, L., Aalbersberg, EA., Geluk-Jonker, MM., et al.[2021]

177Lu-octreotate therapy showed potential effectiveness in treating paragangliomas and meningiomas, with some patients experiencing tumor regression or stable disease, although response rates were lower than in gastroenteropancreatic neuroendocrine tumors.

The treatment did not demonstrate any antitumor effects in patients with small cell lung carcinoma or melanoma, highlighting the need for further studies to confirm these findings due to the small patient sample size.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of therapy with [177Lu-DOTA0, Tyr3]octreotate in patients with paraganglioma, meningioma, small cell lung carcinoma, and melanoma. van Essen, M., Krenning, EP., Kooij, PP., et al.[2013]

The development of a single vial kit for (177) Lu-DOTATATE allows for safe and efficient preparation of this radiopharmaceutical in hospital settings, making it more accessible for treating patients with inoperable neuroendocrine tumors.

Preclinical studies showed that (177) Lu-DOTATATE is rapidly cleared from the body through the kidneys, indicating a favorable biodistribution profile that supports its use in peptide receptor radionuclide therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single vial kit formulation of DOTATATE for preparation of (177) Lu-labeled therapeutic radiopharmaceutical at hospital radiopharmacy. Mukherjee, A., Lohar, S., Dash, A., et al.[2019]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK587368/

Neuroendocrine Tumor 177Lutetium-Dotatate Therapy - NCBI Clinical trials, including the landmark NETTER-1 study, have demonstrated significant improvements in progression-free survival, quality of life ...

2. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/06/05/jnumed.124.269416

Cost-Effectiveness of [177Lu]Lu-DOTATATE for the Treatment ... The NETTER-2 trial found superior median progression-free survival (22.8 mo vs. 8.5 mo) and similar adverse events and quality-of-life measures ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1607427

Phase 3 Trial of 177 Lu-Dotatate for Midgut ... Treatment with 177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04665739

NCT04665739 | Testing Lutetium Lu 177 Dotatate in ... Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. Detailed Description.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11137281/

Long-term clinical outcomes of [177Lu]Lu-DOTATATE in ... They established an estimated median PFS of 36.4 months (about 3 years) and the mean OS was 61.9, 52.2, and 38.4 months (about 3 years) in WHO ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2024/208700s031lbl.pdf

LUTATHERA® (lutetium Lu 177 dotatate) injection, for ... The safety data of LUTATHERA with octreotide was evaluated in NETTER-1 [see ... neuroendocrine tumors (GEP-NETs) was assessed in 360 patients in the ...

7. lutathera-hcp.com lutathera-hcp.com/2l-netter-1-safety

2L: NETTER-1 Safety | HCP The most common grade 3/4 adverse reactions with a higher incidence in the LUTATHERA arm were lymphopenia (44%), increased GGT (20%), vomiting (7%), ...

8. jnm.snmjournals.org jnm.snmjournals.org/content/66/3/449

Dosimetry of [177Lu]Lu-DOTATATE in Patients with Advanced ... This substudy of the phase III NETTER-1 trial evaluated [177Lu]Lu-DOTATATE (hereafter 177Lu-DOTATATE) for advanced midgut neuroendocrine tumors ...

9. lutathera-hcp.com lutathera-hcp.com/1l-netter-2-safety

1L: NETTER-2 Safety - LUTATHERA® (lutetium Lu 177 dotatate) The most common adverse events (≥20% in either arm) were nausea (27% vs 18%), diarrhea (26% vs 34%), and abdominal pain (18% vs 27%) for LUTATHERA + SSA vs ...