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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of a new treatment for neuroendocrine tumors, a type of cancer arising from hormone-producing cells. The goal is to determine a safe dose of 212Pb-VMT-alpha-NET, a medication that uses a radioactive substance to target cancer cells. Researchers will divide participants into groups to test various radiation dose levels. Suitable candidates for this trial include those with neuroendocrine tumors that have not responded to other treatments and have shown tumor growth. As an Early Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatment 212Pb-VMT-alpha-NET is generally safe at certain doses. In one study, patients tolerated doses up to 185 MBq without major issues, and researchers supported increasing the dose to 277.5 MBq. Another report indicated that 55 patients who received at least one treatment with 212Pb-VMT-alpha-NET experienced no serious side effects. Additionally, patients treated with a similar agent, 203Pb-VMT-α-NET, showed no severe adverse effects.

This study is in its early stages, focusing on safety and determining the right dose for future trials. While researchers are testing the treatment for safety, these early findings suggest it is well-tolerated at certain levels. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about 212Pb-VMT-alpha-NET because it offers a new approach for treating neuroendocrine tumors. Unlike typical treatments like surgery, chemotherapy, or peptide receptor radionuclide therapy (PRRT), this treatment uses a radioactive isotope, 212Pb, which targets tumor cells with precision. The unique mechanism involves delivering a potent alpha radiation directly to the cancer cells, potentially minimizing harm to surrounding healthy tissue. This targeted approach could lead to more effective tumor destruction and fewer side effects, making it a promising option for patients.

What evidence suggests that 212Pb-VMT-alpha-NET could be an effective treatment for neuroendocrine tumors?

Research shows that 212Pb-VMT-alpha-NET, the investigational treatment in this trial, may effectively treat neuroendocrine tumors. In earlier studies, 8 out of 12 patients experienced significant tumor shrinkage and symptom improvement. This treatment targets specific parts of tumor cells, delivering radiation directly to the cancer while sparing healthy tissue. Early data suggests it is well-tolerated and effective even at low doses. Preclinical studies have demonstrated that it can slow tumor growth and provide lasting results. While more research is needed, these findings offer hope for its potential use in combating neuroendocrine tumors. ^{1 3 4 6 7}

Who Is on the Research Team?

David Bushnell, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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 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 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]

Citations

1. perspectivetherapeutics.com perspectivetherapeutics.com/pr/perspective-therapeutics-presents-updated-interim-data-from-its-ongoing-phase-12a-clinical-trial-of-212pbvmtnet-at-the-esmo-congress-2025

Press Release Perspective Therapeutics Presents Updated Interim Data from its Ongoing Phase 1/2a Clinical Trial of [212Pb]VMT-α-NET at the ESMO Congress 2025.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3005

[212Pb]VMT-α-NET therapy in somatostatin receptor 2 ... Conclusions: [212Pb]VMT-α-NET is a well-tolerated, next generation RPT showing signs of clinical activity at early dose-levels in this phase 1/ ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/242556

212Pb-VMT-α-NET Targeted Alpha Therapy in Metastatic ... 8 out of the 12 patients showed a marked reduction in functional tumour volume with a significant improvement in symptoms even at this rather ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12397198/

[203/212Pb]Pb-VMT-α-NET as a novel theranostic agent ... Preclinical evaluations have shown that [212Pb]Pb-VMT-α-NET therapies are effective in slowing tumor growth and resulted in complete durable ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.668

Interim safety and efficacy data of [ 212 Pb]VMT-α-NET in ... Conclusions: [212Pb]VMT-α-NET is safe up to 185 MBq (5 mCi) dose level, and the SMC supported dose escalate to cohort 3 at 277.5 MBq (7.5 mCi) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06148636

NCT06148636 | A Safety Study of 212Pb-VMT-alpha-NET ... 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.

7. nanets.net nanets.net/abstracts-archive/2024/2018-c37-wahl-preliminary-safety-and-efficacy-data-of-212pb-vmt-net-in-somatostatin-receptor-2-sstr2-expressing-neuroendocrine-tumors-nets/file

Preliminary safety and efficacy data of [212Pb]VMT-α-NET ... This is a first-in-human dose-escalation study to determine the safety, pharmacokinetics, and preliminary efficacy of [212Pb]VMT-α-NET in adult NETs of any ...