Recruiting
Phase 1

\[212Pb\]VMT-Alpha-NET

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06479811

Conditions

Sinonasal Neuroendocrine Carcinoma

Nasopharyngeal Carcinoma

Esthesioneuroblastoma

Olfactory Neuroblastoma

Somatostatin Receptor Positive

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:

Some cancers have high levels of proteins called somatostatin receptors (SSTRs) on the surface of the tumors. These tumors can be in the lung, head and neck, digestive tract, kidneys, and in or near the adrenal glands. Researchers want to know if drug treatments that target SSTRs can help shrink these types of tumors.

Objective:

To test a study drug (\[212Pb\]VMT-Alpha-NET) in people with tumors that have SSTRs.

Eligibility:

People aged 18 years and older with tumors of the lung, kidneys, head and neck, digestive tract, or adrenal glands that have SSTRs. Their tumors must have spread to other organs and cannot be removed with surgery.

Design:

Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and a test of their heart function. A sample of tumor tissue may be collected if one is not already available.

\[212Pb\]VMT-Alpha-NET is given through a tube attached to a needle inserted into a vein. The drug will be given on the first day of four 8-week cycles. Participants will stay in the hospital for a few nights after each dose. They will have blood tests once a week during 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 up to 6 years after the last treatment.

Conditions

Sinonasal Neuroendocrine Carcinoma

Nasopharyngeal Carcinoma

Esthesioneuroblastoma

Olfactory Neuroblastoma

Somatostatin Receptor Positive

Study ID

NCT06479811

Start date

Aug 19, 2025

Status verified date

Aug 14, 2026

Completion date

Jan 1, 2032

Anticipated

Primary completion date

Jan 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), pheochromocytoma/paraganglioma (PPGL), small cell lung cancers (SCLC), kidney cancers (KC), or Head \& Neck cancers (nasopharyngeal carcinoma \[NPC\], olfactory neuroblastoma \[ONB\], sinonasal neuroendocrine carcinoma \[SNEC\]) that are metastatic or inoperable per Standard of Care. Note: for KC, all histopathologies of kidney cancers are eligible as long as it is a primary renal neoplasm.
  • Required prior therapies:
  • GI NET, PPGL, H\&N: no specific prior therapy is needed.
  • SCLC: At least one prior line of standard of care systemic treatment such as chemotherapy and/or immunotherapy.
  • KC: Renal cell carcinoma (RCC) participants should have received at least one line of prior therapy in the metastatic setting and should have received at least one Programmed cell death protein 1 (PD1) / Programmed death-ligand 1 (PDL1)-targeted immune checkpoint inhibitor as well as one agent targeting the VEGF pathway. Participants with fumarate hydratase (FH) deficient RCC should have received at least one prior line of systemic therapy (such as bevacizumab plus erlotinib). No prior therapy is needed for participants with other histologic subtypes.
  • Have NOT received prior systemic radioligand therapy for definitive therapeutic purposes. Prior external beam radiation therapy is allowed.
  • History of disease progression by imaging (e.g., 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% 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/microliter
  • 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.

  • 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 up to 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:

  • Any investigational agents should be stopped at least 28 days prior to the first dose of \[203Pb\]VMT-Alpha-NET.
  • Systemic therapy should be stopped at least 28 days prior to the first dose of \[203Pb\]VMT-Alpha-NET (participants with prior systemic therapies for their malignancy only, except participants with SCLC).
  • Systemic therapy should be stopped at least 14 days prior to the first dose of \[203Pb\]VMT-Alpha-NET (participants with SCLC only).
  • 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 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

120 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 at different intervals to monitor disease.

[203Pb]VMT-alpha-NET

\[203Pb\]VMT-alpha-NET will be given IV 7 days prior to \[212Pb\]VMT-alpha-NET.

[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 dose expansion. One cycle is 8 weeks.

Primary outcome measure

  • MTD of [212Pb]VMT-alpha-NET (dose escalation cohort) and safety of [212Pb]VMT-alpha-NET at the MTD (dose expansions cohorts) [ Time Frame: DLTs through 12 weeks after initial 212Pb]VMT-alpha-NET administration (dose escalation) and all toxicities from day 1 up through 3 years (dose expansion). ]

Central Contacts and Locations

Central contacts

Jessica K Turner

(240) 858-7554jessica.turner@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

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 alpha Therapy
  • Image-Guided Dosimetry
  • VMT-alpha-NET

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