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

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. ^{1 2 3 4 5}

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. ^{1 4 5 6 7}

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. ^{1 4 5 6 8}

Research Team

Steve Cho, MD

Principal Investigator

University of Wisconsin, Madison

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT. [2019]

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]

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]

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]

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]

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]