Recruiting
Phase 1
Phase 2

\[212Pb\]VMT-alpha-NET

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06427798

Conditions

Somatostatin Receptor Positive

Gastrointestinal Neuroendocrine Tumors

Pheochromocytoma

Paragangliomas

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

68Ga-DOTATATE

[203Pb]VMT-alpha-NET

[212Pb]VMT-alpha-NET

Study Details

Brief summary:

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....

Conditions

Somatostatin Receptor Positive

Gastrointestinal Neuroendocrine Tumors

Pheochromocytoma

Paragangliomas

Study ID

NCT06427798

Start date

Feb 7, 2025

Status verified date

Aug 14, 2026

Completion date

Jul 1, 2039

Anticipated

Primary completion date

Jul 1, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

  • INCLUSION CRITERIA:
  • Participants must have histopathologically confirmed gastrointestinal neuroendocrine tumors (GI NET) or pheochromocytoma/paraganglioma (PPGL) cancers that are metastatic or inoperable per Standard of Care.
  • Have received at least 1 prior systemic radioligand therapy for definitive therapeutic purposes. Note: Participants with prior external beam radiation treatment (EBRT) will also be eligible as long as they have had at least 1 prior administration of a systemic radioligand therapy.
  • Must have at least 1 measurable lesion by RECIST 1.1 (phase II only).
  • History of progression by imaging per RECIST 1.1 or clinically (defined as increase in severity or frequency of symptoms related to disease) within the past 36 months prior to the first dose of \[203Pb\]VMT-alpha-NET.
  • Evidence of somatostatin receptors (SSTR) expression on at least 50 percent of the radiographically identifiable (i.e., visible on an anatomic scan such as CT or magnetic resonance imaging \[MRI\]) tumor, as indicated by a positive (uptake qualitatively identifiable as above the local background) on SSTR PET scan.
  • Age >= 18 years.
  • ECOG performance status <= 1.
  • Participants must have adequate organ and marrow function as defined below:

  • Leukocytes: 3,000/microliter
  • Absolute Neutrophil Count: 1,500/microliter
  • Platelets: 100,000/miroliter
  • Hemoglobin: >= 9.0 g/dL
  • Total bilirubin: within normal institutional limits. Note: <= 5 X institutional upper limit of normal (ULN) if bilirubin elevation is due to a benign process such as Gilbert syndrome
  • AST: <= 2.5 X institutional ULN
  • ALT: <= 2.5 X institutional ULN
  • Creatinine: within normal institutional limits

OR

  • Calculated creatinine clearance (glomerular filtration rate (eGFR): >= 60 mL/min/1.73 m\^2 for participants with creatinine levels above institutional normal

  • Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression at screening.
  • Participants with new or progressive brain metastases or leptomeningeal disease are eligible as long as the participant is asymptomatic and not requiring medication for symptom control from the brain lesions at screening.
  • Participants seropositive for human immunodeficiency virus (HIV) must:
  • be on effective anti-retroviral therapy; and
  • have an undetectable viral load at screening.
  • Participants seropositive for hepatitis B virus (HBV), must have HBV viral load undetectable at screening.

-Participants seropositive for hepatitis C virus (HCV) must:
  • received curative treatment; and
  • have an undetectable HCV viral load at screening.

  • Participants may enroll in this study while on another therapeutic trial in order to start the screening process. However, all other investigational agents should be stopped at least 28 days prior to receiving \[203Pb\]VMT-alpha-NET.
  • Individuals of child-bearing potential (IOCBP) and individuals who can father children must agree to use an effective method of contraception (barrier, hormonal, intrauterine device \[IUD\], surgical sterilization, abstinence) at study entry and at least 6 months after the last dose of the study agent(s).
  • Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study agents.
  • The ability of the participant to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to VMT-alpha-NET.
  • Positive Beta human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test performed in i IOCBP at screening.
  • QTc > 450 ms on electrocardiogram (EKG) at screening. Note: Framingham correction for QTc will be used.
  • History of or detection at screening of active/untreated secondary malignancy except nonmelanoma skin cancer and carcinoma in situ of the uterine cervix.
  • Uncontrolled intercurrent illness, factors, evaluated by medical history and physical exam which would potentially increase in the risk of the participant.

Study Design

Enrollment

66 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 1/Dosimetry Arm 1

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

experimental: 2/Arm 2

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

experimental: 3/Arm 3

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

Interventions

68Ga-DOTATATE

68Ga-DOTATATE PET/CT whole-body scanning will be done at target dose of 5 mCi. The whole-body PET/CT scan will be started approximately 60 minutes after the tracer injection and will take up to 2 hours.

[203Pb]VMT-alpha-NET

\[203Pb\]VMT-alpha-NET (6 mCi) will be given IV at 7 days prior.

[212Pb]VMT-alpha-NET

\[212Pb\]VMT-alpha-NET will be given IV on Day 1 of every cycle for 4 cycles total at escalating doses in Phase I and at MTD during Phase II. One cycle is 8 weeks.

Primary outcome measure

  • Phase I: MTD of [212Pb]VMT-alpha-NET using a 3+3 dose escalation design in GI NET and PPGL in a re-treatment setting [ Time Frame: DLT period (through 12 weeks after initial 212Pb]VMT-alpha-NET administration). ]
  • Phase II: ORR by RECIST 1.1 of participants treated with [212Pb]VMT-alpha-NET at the MTD at the completion of 4 cycles of treatment, reported by disease groups [ Time Frame: Baseline until progression or 6 years after receiving the first infusion of study drug. ]

Central Contacts and Locations

Central contacts

Joy H Zou, R.N.

(240) 760-6153joy.zou@nih.gov

Frank I Lin, M.D.

(240) 760-6166frank.lin2@nih.gov

Locations

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20892

Contacts

Joy Zou, R.N.

240-760-6153joy.zou@nih.gov

National Cancer Institute Referral Office

(888) 624-1937ncimo_referrals@mail.nih.gov

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Aug 18, 2026

Last verified

Aug 14, 2026

Keywords

  • 212Pb
  • Targeted Therapies
  • Image-Guided Dosimetry
  • VMT- -NET

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-08-18.