Study of [212Pb]VMT-alpha-NET for GI Neuroendocrine Tumors and Pheochromocytoma/Paraganglioma
This study is testing a new treatment called [212Pb]VMT-alpha-NET for people with gastrointestinal neuroendocrine tumors (GI NET) or pheochromocytoma/paraganglioma (PPGL) that have spread or cannot be removed by surgery. These cancers have high levels of a protein called somatostatin receptors (SSTR) on their surface. The drug, [212Pb]VMT-alpha-NET, is designed to attach to these SSTRs and deliver a radioactive agent to kill the cancer cells. To join, you must be an adult (18-120 years old) with confirmed GI NET or PPGL that is metastatic or inoperable, and you must have already received at least one other systemic radioligand therapy. The study aims to find the safest and most effective dose of [212Pb]VMT-alpha-NET and see how many participants respond to the treatment.
- Study design
- This study plans to enroll 66 participants and involves escalating doses of the study drug in Phase I, followed by a maximum tolerated dose in Phase II.
- What's involved
- You will receive [212Pb]VMT-alpha-NET intravenously (IV) on Day 1 of every 8-week cycle, for a total of 4 cycles. You will also have a 68Ga-DOTATATE PET/CT scan and an IV dose of [203Pb]VMT-alpha-NET before starting the main treatment.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your progress will be monitored from the start of treatment until your disease progresses or for up to 6 years after receiving the first infusion of the study drug.
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NCT06427798
Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy
Recruiting
PHASE1Ages 18+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~66 participants
Updated 2026-08-18 on ClinicalTrials.gov
What's tested:68Ga-DOTATATE[203Pb]VMT-alpha-NET[212Pb]VMT-alpha-NET
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
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
Measured over DLT period (through 12 weeks after initial 212Pb]VMT-alpha-NET administration).
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Frank I Lin, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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
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.
What this trial measures
- Phase I: MTD of [212Pb]VMT-alpha-NET using a 3+3 dose escalation design in GI NET and PPGL in a re-treatment settingDLT period (through 12 weeks after initial 212Pb]VMT-alpha-NET administration).
The MTD will be presented as a recommended dose to be used as the recommended phase II dose (RP2D) for the combined participant population, as well as for each disease group being studied (GI-NET, PPGL).
- 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 groupsBaseline until progression or 6 years after receiving the first infusion of study drug.
The overall response rate will be presented as a percentage along with 95% confidence intervals. Only evaluable participants will be included.