Lutetium-177 Therapy for Neuroendocrine Tumors

(LUMOD-ID Trial)

Overseen By Stephen A Graves, Ph.D., DABR

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Iowa

Disqualifiers: Pregnancy, Active infection, Heart failure, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 32 weeks

120 Participants Needed

Trial Summary

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. ^{1 2 3 4 5}

Is 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. ^{1 2 3 6 7}

What 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. ^{1 2 3 4 8}

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.

Research Team

Stephen Graves, Ph.D., DABR

Principal Investigator

University of Iowa

Eligibility 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

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.

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

Treatment Details

Interventions

• Lutetium Lu 177 dotatate therapy

Trial Overview 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.

Participant Groups

Group I: Dosimetry-based lutetium Lu 177 dotatate therapy Experimental Treatment 1 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 dotatate Active Control 1 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

Who Is Running the Clinical Trial?

University of Iowa

Lead Sponsor

Trials

486

Recruited

934,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

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]

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]

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 phase 2 clinical trial involving 37 patients with progressive gastroenteropancreatic neuroendocrine tumors, treatment with Lutetium (177) DOTATATE showed that 28% of patients had a partial response and 41% had stable disease, indicating effective disease control.

The therapy was well tolerated with no significant acute or delayed toxicity observed, and it led to improvements in patients' performance status and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Delpassand, ES., Samarghandi, A., Zamanian, S., et al.[2022]

Treatment with (177)Lu-DOTATATE, a radiolabelled somatostatin analogue, shows promising results in managing inoperable or metastasized neuroendocrine tumors, with significant tumor regression and a median progression-free survival of over 40 months.

The therapy is associated with few and mild side effects, especially when kidney-protective agents are used, and it significantly improves patients' quality of life, suggesting it could become a first-choice treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-labelled peptides for therapy of neuroendocrine tumours. Kam, BL., Teunissen, JJ., Krenning, EP., et al.[2022]

Lutetium Lu-177 dotatate is an effective treatment for gastroenteropancreatic neuroendocrine tumors, significantly improving progression-free survival, as shown in European studies.

In a study of 12 patients, tumor flare reactions were observed in 5 patients, but these reactions can be effectively managed with corticosteroids or other strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu-177 Dotatate Flare Reaction. Salner, AL., Blankenship, B., Dunnack, H., et al.[2022]

A study of 32 administrations of [177Lu]Lu-DOTA-TATE showed that using lead aprons significantly reduced radiation exposure for medical staff, with reductions of up to 71% for physicians and 68% for nurses.

The average radiation dose measured was consistent across different monitoring methods, indicating that with proper safety measures, administering [177Lu]Lu-DOTA-TATE can be done safely, although regular monitoring is essential to stay within annual dose limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. Riveira-Martin, M., Struelens, L., Muñoz Iglesias, J., et al.[2023]

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]

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. 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]

3. 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]

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

Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Lutetium-labelled peptides for therapy of neuroendocrine tumours. [2022]

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

Lutetium Lu-177 Dotatate Flare Reaction. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Radiation exposure assessment of nuclear medicine staff administering [177Lu]Lu-DOTA-TATE with active and passive dosimetry. [2023]

8. 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]