212Pb-VMT-alpha-NET for Neuroendocrine Tumors

Overseen By Yusuf Menda, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: David Bushnell

Must be taking: Somatostatin analogues

Must not be taking: Investigational drugs

Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-10 weeks

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a safety study to determine the recommended dose to test in clinical trials. The study involves two treatments with 212Pb (212-lead) VMT-α-NET. This is a safety study only; it will most likely not provide therapeutic benefit.

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, you must comply with your antihypertensive medications if prescribed and refrain from 'natural' or 'herbal' supplements unless approved by the treating physician and research team.

What data supports the effectiveness of the treatment 212Pb-VMT-alpha-NET for neuroendocrine tumors?

The research shows that similar treatments, like peptide receptor radionuclide therapy (PRRT) with Lutathera, have been effective in treating neuroendocrine tumors by controlling tumor growth and improving patient outcomes. Additionally, a study using a related compound, 203Pb-VMT-alpha-NET, demonstrated high uptake in liver metastases, suggesting potential effectiveness for 212Pb-VMT-alpha-NET. ^{1 2 3 4 5}

Is 212Pb-VMT-alpha-NET safe for humans?

The research on 212Pb-VMT-alpha-NET for neuroendocrine tumors is still in early stages, and while it shows promise in targeting tumors, further studies are needed to confirm its safety in humans. ^{1 2 3 5 6}

How does the drug 212Pb-VMT-alpha-NET differ from other treatments for neuroendocrine tumors?

The drug 212Pb-VMT-alpha-NET is unique because it uses targeted alpha therapy (TAT) with lead-212, which delivers high-energy radiation directly to tumor cells, potentially improving effectiveness compared to traditional treatments. This approach aims to enhance tumor targeting while minimizing damage to surrounding healthy tissues. ^{1 6 7 8 9}

Research Team

David Bushnell, MD

Principal Investigator

University of Iowa

Eligibility Criteria

This trial is for adults aged 18-80 with well-differentiated neuroendocrine tumors who've had prior treatments and show no immediate response. They must be willing to follow the study's procedures, have a good performance status, not have other active cancers needing treatment, and agree to use effective contraception.

Inclusion Criteria

My condition cannot be cured and has worsened despite all known beneficial treatments.

I have previously undergone PRRT treatment.

Stated willingness to comply with all study procedures and availability for duration of study

Exclusion Criteria

I haven't taken any experimental drugs in the last 4 weeks.

I have a history of heart failure and my heart's pumping ability is reduced.

I haven't had any cancer treatment, including radiation, in the last 2 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two treatments with 212Pb VMT-α-NET, approximately 8 to 10 weeks apart, with infusions of amino acids and medications to protect against nausea

8-10 weeks

Follow-up

Participants are monitored for safety assessments including blood and urinary tests, and imaging to measure tumor response

6 months

Long-term follow-up

Participants will have lifelong follow-up for safety and effectiveness assessments

Treatment Details

Interventions

• 212Pb-VMT-alpha-NET

Trial Overview The safety of two treatments using a radioactive substance called [212Pb] VMT-α-NET is being tested. The goal is to find the right dose for future trials. This study focuses on safety rather than therapeutic benefit.

Participant Groups

Group I: Cohort 4 Experimental Treatment 2 Interventions

If the participants from Cohort 3 tolerate therapy, new participants are enrolled and are prescribed \[212Pb\] VMT-α-NET with the total radiation dose to kidneys not to exceed 1050 cGy.

Group II: Cohort 3 Experimental Treatment 2 Interventions

If the participants from Cohort 2 tolerate therapy, new participants are enrolled and are prescribed \[212Pb\] VMT-α-NET with the total radiation dose to kidneys not to exceed 810 cGy.

Group III: Cohort 2 Experimental Treatment 2 Interventions

If the participants from Cohort 1 tolerate therapy, new participants are enrolled and are prescribed \[212Pb\] VMT-α-NET with the total radiation dose to kidneys not to exceed 600 cGy.

Group IV: Cohort 1 Experimental Treatment 2 Interventions

This is the starting dose level for participants. Participants are prescribed \[212Pb\] VMT-α-NET with the total radiation dose to kidneys not to exceed 350 cGy.

Group V: -1 Dose Level Experimental Treatment 2 Interventions

This dose level is used if the starting dose level is deemed to have unacceptable toxicity. Participants are prescribed \[212Pb\] VMT-α-NET with the total radiation dose to kidneys not to exceed 200 cGy.

Who Is Running the Clinical Trial?

David Bushnell

Lead Sponsor

Trials

4

Recruited

50+

Holden Comprehensive Cancer Center

Collaborator

Trials

27

Recruited

710+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Perspective Therapeutics

Industry Sponsor

Trials

6

Recruited

710+

Findings from Research

Combining peptide receptor radionuclide therapy (PRRT) with anti-PD1 immunotherapy significantly enhances treatment response in neuroendocrine tumors (NETs), with the most effective approach being to administer PRRT before anti-PD1 therapy.

In a study involving 96 mice with human NET cells, the early PRRT regimen led to the greatest reduction in tumor size and increased T-cell activation, indicating a robust inflammatory response compared to other treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of Peptide Receptor Radiotherapy to Immune Checkpoint Inhibition Therapy Improves Outcomes in Neuroendocrine Tumors. Esfahani, SA., De Aguiar Ferreira, C., Summer, P., et al.[2023]

In a study involving 35 patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with Lutathera (177Lu-DOTATATE), the treatment was well tolerated, with most adverse events being low grade.

Among patients who completed all 4 cycles of Lutathera, 22% showed a partial response, 44% had stable disease, and 13% experienced disease progression, indicating Lutathera's potential efficacy in managing GEP-NETs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting. Mejia, A., Vivian, E., Nwogu, C., et al.[2023]

In a patient with advanced midgut neuroendocrine tumor and carcinoid heart disease, the use of 203 Pb-VMT-α-NET showed high uptake in liver metastases, indicating its potential effectiveness for targeted therapy.

The imaging results from 203 Pb-VMT-α-NET were comparable to those from 68 Ga-HA-DOTATATE PET/CT, suggesting that 203 Pb-VMT-α-NET could be a feasible option for therapy in patients who are refractory to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

203 Pb-VMT-α-NET Scintigraphy of a Patient With Neuroendocrine Tumor. Müller, D., Herrmann, H., Schultz, MK., et al.[2023]

Neuroendocrine tumors (NETs) are challenging to diagnose and treat due to their low incidence and high variability, with treatment decisions often made in specialized cancer centers.

Among various treatment options, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE stands out as the only method that can effectively control symptoms, halt tumor growth, and improve both progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Patients with Neuroendocrine Neoplasia-Evidence-Based Approaches and New Horizons. Bundschuh, RA., Habacha, B., Lütje, S., et al.[2020]

In a study of 43 patients with advanced gastrointestinal neuroendocrine tumors, (177)Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) demonstrated an 84% disease control rate, with a median response duration of 25 months and a median progression-free survival of 36 months.

Both standard and reduced dosages of Lu-PRRT were found to be safe, as none of the patients experienced side effects, even those at higher risk for kidney or bone marrow toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. Paganelli, G., Sansovini, M., Ambrosetti, A., et al.[2022]

Targeted alpha therapy (TAT) using lead-212 (212Pb) shows promise for treating neuroendocrine tumors (NETs), with the study identifying [212Pb]Pb-eSOMA-01 as a leading candidate based on its high tumor uptake and low kidney absorption in tests with tumor-bearing mice.

The ligands developed for this therapy demonstrated high radiochemical yields and stability, with [212Pb]Pb-eSOMA-01 achieving the highest absorbed dose in tumors (35.49 Gy/MBq) while minimizing exposure to healthy tissues, indicating a potential for safer and more effective treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. Chapeau, D., Koustoulidou, S., Handula, M., et al.[2023]

In a study of 11 patients with grade 1/2 metastatic neuroendocrine tumors treated with [225Ac]Ac-DOTATATE, the therapy demonstrated a high disease control rate of 89%, with 44.4% of patients showing a partial response and 44.4% having stable disease.

The treatment was found to be stable and safe, with only mild toxicities reported (grade 2 renal and hematotoxicity), and a median progression-free survival of 12 months, indicating its potential effectiveness for patients who were refractory to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. Demirci, E., Alan Selçuk, N., Beydağı, G., et al.[2023]

A 46-year-old man with rectal neuroendocrine tumors and extensive skeletal metastases was treated with 6 cycles of 225Ac-DOTATATE, showing excellent symptomatic, biochemical, and radiological responses without severe adverse events.

The use of 225Ac-DOTATATE as a first-line treatment offers a promising new strategy for patients with metastatic neuroendocrine tumors who have a high burden of skeletal disease, potentially overcoming the limitations of traditional β-emitter therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha Before Beta: Exceptional Response to First-Line 225Ac-DOTATATE in a Patient of Metastatic Neuroendocrine Tumor With Extensive Skeletal Involvement. Satapathy, S., Sood, A., Das, CK., et al.[2023]

Pancreatic neuroendocrine tumors (PNETs) can be functional or nonfunctional, with functional tumors causing distinctive symptoms and nonfunctional tumors often being diagnosed later due to their size; their prognosis varies widely based on histologic grade and biological behavior.

Treatment options for symptomatic advanced PNETs include long-acting somatostatin analogues and peptide receptor radionucleotide therapy (PRRT) for somatostatin receptor-positive tumors, along with systemic therapies like cytotoxic agents and biologic agents targeting specific signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging therapies for pancreas neuroendocrine cancers. Mahjoub, AR., O'Reilly, EM.[2020]

References

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

Addition of Peptide Receptor Radiotherapy to Immune Checkpoint Inhibition Therapy Improves Outcomes in Neuroendocrine Tumors. [2023]

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

Peptide receptor radionuclide therapy implementation and results in a predominantly gastrointestinal neuroendocrine tumor population: A two-year experience in a nonuniversity setting. [2023]

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

203 Pb-VMT-α-NET Scintigraphy of a Patient With Neuroendocrine Tumor. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Therapy of Patients with Neuroendocrine Neoplasia-Evidence-Based Approaches and New Horizons. [2020]

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

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

[212Pb]Pb-eSOMA-01: A Promising Radioligand for Targeted Alpha Therapy of Neuroendocrine Tumors. [2023]

7. Turkey pubmed.ncbi.nlm.nih.gov

Initial Findings on the Use of [225Ac]Ac-DOTATATE Therapy as a Theranostic Application in Patients with Neuroendocrine Tumors. [2023]

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

Alpha Before Beta: Exceptional Response to First-Line 225Ac-DOTATATE in a Patient of Metastatic Neuroendocrine Tumor With Extensive Skeletal Involvement. [2023]

9. China pubmed.ncbi.nlm.nih.gov

Emerging therapies for pancreas neuroendocrine cancers. [2020]