[212Pb]VMT-alpha-NET for Neuroendocrine Tumors

Overseen By Joy H Zou, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Radioligand therapy

Disqualifiers: Allergic reactions, Pregnancy, Secondary malignancy, others

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

Compensation: Varies

Number of Visits: 9

Duration: 32 weeks

66 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that all other investigational agents should be stopped at least 28 days before receiving the study drug. It's best to discuss your specific medications with the trial team.

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

Research shows that similar treatments using lead-212 (212Pb) for neuroendocrine tumors have shown promising results, with high tumor uptake and effectiveness in targeting cancer cells. This suggests that [212Pb]VMT-alpha-NET could also be effective in treating neuroendocrine tumors. ^{1 2 3 4 5}

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

The research does not provide specific safety data for [212Pb]VMT-alpha-NET in humans, but it mentions that similar treatments like Lutathera (177Lu-DOTATATE) are generally well tolerated in patients with neuroendocrine tumors. Further studies are needed to confirm the safety of [212Pb]VMT-alpha-NET. ^{1 2 5 6 7}

How is the drug [212Pb]VMT-alpha-NET different from other treatments for neuroendocrine tumors?

[212Pb]VMT-alpha-NET is unique because it uses targeted alpha therapy (TAT) with lead-212, which is a type of radiation therapy that delivers high-energy particles directly to the tumor, potentially offering more precise treatment with less damage to surrounding healthy tissue compared to traditional therapies. ^{1 2 5 8 9}

What is the purpose of this trial?

Background: Gastrointestinal neuroendocrine tumors (GI NET) are a type of cancer that affects the stomach and intestines; pheochromocytoma/paragangliomas (PPGL) are tumors that grow in or near the adrenal glands. Both of these types of tumor have high levels of a protein called somatostatin receptors (SSTR) on their surfaces. Researchers want to test a treatment that targets SSTR. Objective: To test a drug (\[212Pb\]VMT-alpha-NET) in people with GI NET or PPGL. The drug has 2 components: a protein to bind to SSTR and a radioactive agent to kill the cancer cells. Eligibility: Adults aged 18 years or older with GI NET or PPGL tumors that have spread and cannot be removed with surgery. Design: Participants will be screened. They will have a physical exam, with imaging scans, blood tests, and tests of their heart function. \[212Pb\]VMT-alpha-NET is given through a tube attached to a needle inserted into a vein (infusion). Treatment will be given in four 8 week cycles. Participants will receive the drug on the first day of each cycle. They will remain in the clinic at least 4 hours after each infusion and may need to stay in the hospital for up to 48 hour for monitoring and testing. They will have blood tests every week of each cycle. Some participants will also get a related study drug (\[203Pb\]VMT-alpha-NET). They will receive this drug a few days before the first 2 cycles. At 4, 24, and 48 hours after each infusion, they will have whole body scans. These scans will show where the study drug went in their body. Follow-up visits will continue for 10 years....

Research Team

Frank I Lin, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults with gastrointestinal neuroendocrine tumors or pheochromocytoma/paragangliomas that have spread and can't be surgically removed. They must have been previously treated with targeted radioligand therapy.

Inclusion Criteria

Must have at least 1 measurable lesion by RECIST 1.1 (phase II only)

My cancer has worsened in the last 3 years as shown by tests or symptoms.

My brain scans show no signs of cancer growth after treatment for brain metastases.

Exclusion Criteria

Uncontrolled intercurrent illness or factors evaluated by medical history and physical exam which would potentially increase the risk of the participant

I have no active secondary cancers except for skin cancer or cervical carcinoma in situ.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to VMT-alpha-NET

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive [212Pb]VMT-alpha-NET in four 8-week cycles, with infusions on the first day of each cycle and monitoring for up to 48 hours post-infusion

32 weeks

4 visits (in-person) per cycle, weekly blood tests

Dosimetry

A subset of participants receive [203Pb]VMT-alpha-NET for imaging and dosimetry studies before the first two cycles

16 weeks

Additional visits for imaging at 4, 24, and 48 hours post-infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, with visits approximately 30 days post-treatment, every 12 weeks for years 1-3, every 6 months for years 4-6, and annually thereafter

10 years

Treatment Details

Interventions

• [212Pb]VMT-alpha-NET

Trial Overview [212Pb]VMT-alpha-NET, a drug combining a protein targeting somatostatin receptors on cancer cells with a radioactive agent to destroy them, is being tested over four 8-week cycles of infusion treatments.

Participant Groups

Group I: 3/Arm 3 Experimental Treatment 2 Interventions

\[212Pb\]VMT-alpha-NET at MTD.

Group II: 2/Arm 2 Experimental Treatment 2 Interventions

Escalating doses of \[212Pb\]VMT-alpha-NET.

Group III: 1/Dosimetry Arm 1 Experimental Treatment 3 Interventions

Escalating doses of \[212Pb\]VMT-alpha-NET, imaging with \[203Pb\]VMT-alpha-NET.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 32 patients with advanced metastatic GEP-NETs who were refractory to 177Lu-DOTATATE therapy, 225Ac-DOTATATE targeted alpha therapy showed promising efficacy, with 15 patients achieving partial remission and no documented disease progression during a median follow-up of 8 months.

The therapy also resulted in a significant decrease in plasma chromogranin levels, indicating a biochemical response, and suggests that 225Ac-DOTATATE could be a valuable treatment option for patients who have exhausted other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. Ballal, S., Yadav, MP., Bal, C., et al.[2022]

Neuroendocrine neoplasms (NEN), particularly well-differentiated types, can be effectively diagnosed and treated using peptide receptor radionuclide therapy (PRRT) with somatostatin receptor analogues, which have been shown to be a safe and effective treatment option following FDA and EMA approval of 177Lu-DOTATATE.

Current research is focused on enhancing the efficacy of PRRT and minimizing its toxicity through personalized treatment approaches, improved patient selection, and the development of new radiopharmaceuticals, indicating a promising future for NEN management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging Theranostics of Neuroendocrine Tumors. Fortunati, E., Bonazzi, N., Zanoni, L., et al.[2023]

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 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]

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]

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]

References

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

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Germany pubmed.ncbi.nlm.nih.gov

Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. [2022]

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

Molecular imaging Theranostics of Neuroendocrine Tumors. [2023]

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

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

6. 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]

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. Germany pubmed.ncbi.nlm.nih.gov

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

9. 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]