[212Pb]VMT-Alpha-NET in Metastatic or Inoperable Somatostatin-Receptor Positive Gastrointestinal Neuroendocrine Tumors, Pheochromocytoma/Paragangliomas, Small Cell Lung, Renal Cell, and Head and Neck Cancers

NCT06479811 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001709001709-C
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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

Pheochromocytoma/Paragangliomas; Head and Neck Tumors; Kidney Cancers; Small Cell Lung Cancers; Gastrointestinal Neuroendocrine Tumors; Somatostatin Receptor Positive

Keywords

212Pb; Targeted alpha Therapy; Image-Guided Dosimetry; VMT-alpha-NET

Outcome Measures

Primary Outcomes (1)

• MTD of [212Pb]VMT-alpha-NET (dose escalation cohort) and safety of [212Pb]VMT-alpha-NET at the MTD (dose expansions cohorts)

  The MTD will be presented as a recommended dose to be used in Dose Expansion Part for each disease group being studied.Descriptive tabulations of toxicity will be provided in Dose Expansion Part, along with the agent attribution determination and CTCAE grade for each toxicity event. The data will be presented as an absolute count of the event at a participant level as well as a percentage of total evaluable participants.

  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).

Secondary Outcomes (6)

• Overall Response Rate

  Baseline, weeks 12 and 32 during treatment, every 12 weeks after that until progression or 3 years after the first [203Pb]VMT-alpha-NET infusion.

• Progression Free Survival

  Baseline until progression or 6 years after receiving the first infusion of study drug

• Safety of [203Pb]VMT-alpha-NET (dose escalation cohort) and [212Pb]VMT-alpha-NET

  Study duration

• Overall Survival

  Baseline until progression or 6 years after receiving the first infusion of study drug

• PK properties of [212Pb]VMT-alpha-NET via blood and urine sampling

  After every infusion of [212Pb]VMT-alpha-NET

Study Arms (3)

1/Dosimetry Arm 1

EXPERIMENTAL

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

Drug: 68Ga-DOTATATE; Drug: [203Pb]VMT-alpha-NET; Drug: [212Pb]VMT-alpha-NET

2/Arm 2

EXPERIMENTAL

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

Drug: 68Ga-DOTATATE; Drug: [212Pb]VMT-alpha-NET

3/Arm 3

EXPERIMENTAL

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

Drug: 68Ga-DOTATATE; Drug: [212Pb]VMT-alpha-NET

Interventions

68Ga-DOTATATE DRUG

68Ga-DOTATATE PET/CT whole-body scanning will be done at at different intervals to monitor disease.

1/Dosimetry Arm 1; 2/Arm 2; 3/Arm 3

[203Pb]VMT-alpha-NET DRUG

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

1/Dosimetry Arm 1

[212Pb]VMT-alpha-NET DRUG

\[212Pb\]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.

1/Dosimetry Arm 1; 2/Arm 2; 3/Arm 3

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Head and Neck Neoplasms; Kidney Neoplasms; Pheochromocytoma; Paraganglioma

Interventions

gallium Ga 68 dotatate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Study Officials

• Frank I Lin, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joy H Zou, R.N.

CONTACT

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

Frank I Lin, M.D.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: June 28, 2024
• Study Start: August 19, 2025
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2032
• Last Updated: April 28, 2026

Record last verified: 2026-04-16

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data from this study may be requested by other researchers after the completion of the primary endpoint.
• Access Criteria: Data from this study may be requested by contacting the PI.

Locations

US (1)