A Safety Study of 212Pb-VMT-alpha-NET in Patients With Neuroendocrine Tumors

NCT06148636 | Active Not Recruiting Early Phase 1 DMC FDA Drug

• 2 other identifiers: 202206110R01CA243014
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroendocrine Tumor of the Lung; Neuroendocrine Tumors; Neuroendocrine Tumor Grade 1; Neuroendocrine Tumor Grade 2; Neuroendocrine Tumor of Pancreas

Keywords

alpha therapy; recurrent disease; theranostics; nuclear medicine

Outcome Measures

Primary Outcomes (1)

• Determine recommended therapeutic dose of [212Pb] VMT-α-NET

  Determine the recommended phase 2 dose for therapy with \[212Pb\]VMT-Α-NET administered intravenously to patients with neuroendocrine tumors that have progressed despite therapy.

  From study day 1 through 6 months post-treatment

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  At 6 months post-treatment

• Maximum tolerated radiation dose for kidneys

  From study day 1 through 12 months post treatment

Study Arms (5)

-1 Dose Level

EXPERIMENTAL

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.

Drug: [212Pb] VMT-α-NET; Diagnostic Test: [203Pb] VMT-α-NET SPECT/CT

Cohort 1

EXPERIMENTAL

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.

Drug: [212Pb] VMT-α-NET; Diagnostic Test: [203Pb] VMT-α-NET SPECT/CT

Cohort 2

EXPERIMENTAL

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.

Drug: [212Pb] VMT-α-NET; Diagnostic Test: [203Pb] VMT-α-NET SPECT/CT

Cohort 3

EXPERIMENTAL

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.

Drug: [212Pb] VMT-α-NET; Diagnostic Test: [203Pb] VMT-α-NET SPECT/CT

Cohort 4

EXPERIMENTAL

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.

Drug: [212Pb] VMT-α-NET; Diagnostic Test: [203Pb] VMT-α-NET SPECT/CT

Interventions

[212Pb] VMT-α-NET DRUG

Up to 2 infusions with \[212Pb\] VMT-α-NET, each infusion separated by at least 8 weeks. During each infusion, the participants also receive an infusion with lysine and arginine (amino acids) to help reduce kidney damage.

-1 Dose Level; Cohort 1; Cohort 2; Cohort 3; Cohort 4

[203Pb] VMT-α-NET SPECT/CT DIAGNOSTIC_TEST

The \[203Pb\] VMT-α-NET SPECT/CT is performed for all participants to determine trial eligibility as well as for the calculations to determine the estimated radiation dose to kidneys. This involves three imaging sessions of about 2 hours each over 2 days. The participants also receive an infusion with lysine and arginine (amino acids) to help reduce kidney damage at the time they receive the injection of . \[203Pb\] VMT-α-NET, a radioactive tracer drug.

-1 Dose Level; Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and willingness to provide informed consent
• Stated willingness to comply with all study procedures and availability for duration of study
• Aged ≥ 18 years to 80 years at the time of study drug administration
• Pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be a well-differentiated neuroendocrine tumor (i.e. grade 1 or grade 2)
• Disease not amenable to curative intent treatment (e.g., surgery) and in addition, has shown either clinical or radiographic progression on all available therapies known to confer clinical benefit in the opinion of the referring physician. If a patient is suspected of experiencing a clinical non-response to current treatment (i.e., the patients clinical symptomatology has not improved despite treatment) the patient may be included if confirmed by the study investigator.
• Prior peptide receptor radionuclide therapy (PRRT)
• Positive somatostatin receptor (SSTR) PET/CT utilizing an FDA approved agent within 12 months prior to anticipated day 1 of treatment demonstrating SSTR positive tumor sites.
• ≥1 evaluable site of disease measuring ≥ 1.0 cm in diameter on CT or MRI as measured per RECIST
• Adequate performance status (ECOG of 0 or 1; or KPS of ≥70).
• No other active malignancy that requires immediate treatment. Slow growing concurrent cancers (such as prostate cancer) are acceptable with appropriate documentation from their treating oncologists for that primary.
• Not experiencing an uncontrolled intercurrent illness such as: infection requiring inpatient admission, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness/social situations, or any other condition that would limit compliance with study requirements as determined by study team members.
• Agreement to adhere to Lifestyle Considerations throughout study duration:
• During this study, participants are asked to:
• Refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice, \[pomelos, exotic citrus fruits, grapefruit hybrids, or fruit juices\] from the day prior to therapy through 5 days post-treatment.
• Comply with their antihypertensive medications, if prescribed.

You may not qualify if:

• Platelets \< 100,000 k/mm3
• Absolute neutrophil count (ANC) of \< 1500 cells/mm3
• Total bilirubin ≥ 2.5x institutional upper limit of normal for age and weight
• Aspartate aminotransferase (AST) \> 2.5 x the institutional upper limit of normal
• Alanine aminotransferase (ALT)\> 2.5 x the institutional upper limit of normal
• eGFR \< 50 mL/min/1.73 m2 (using the Cockcroft Gault formula)
• Proteinuria grade 2 (i.e., ≥ 3+ proteinuria)
• Individuals who are pregnant or breast feeding. A pregnancy test will be administered to individuals of child-bearing potential (per institutional policies) at screening. Participants must agree to pregnancy tests prior to each administration of a radionuclidic agent for this study.
• Individuals of reproductive potential who decline to use effective contraception through the study. Contraception should only be stopped after a conversation with the attending oncologist.
• Lactating individuals who decline to withhold breastfeeding their child. Participants may not breast feed during this study and should only resume after the study in consultation with their oncologist.
• Patient with increased fall risk in the opinion of healthcare professionals
• Therapy (including radiation therapy) within 2 calendar weeks of the start of study therapy. (Toxicities from prior therapies should have resolved to ≤ CTCAE grade 1 or a new baseline established).
• Therapeutic investigational drug within 4 weeks of C1D1 (imaging agents are acceptable)
• History of congestive heart failure and cardiac ejection fraction ≤ 40%
• Patients for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk.

Sponsors & Collaborators

• David Bushnell: lead
• Holden Comprehensive Cancer Center: collaborator
• National Cancer Institute (NCI): collaborator
• Perspective Therapeutics: collaborator

Study Sites (1)

Holden Comprehensive Cancer Center at the University of Iowa

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors; Adenoma, Islet Cell; Recurrence

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenoma; Neoplasms, Glandular and Epithelial; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David Bushnell, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 3 + 3 dose escalation

Study Record Dates

• First Submitted: November 20, 2023
• First Posted: November 28, 2023
• Study Start: November 10, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Upon completion of study.
• Access Criteria: Data Usage Agreement (DUA) must be executed between University of Iowa and requestor/requestor's organization.

Locations

US (1)