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
Phase I/II Trial of Systemic Targeted Radioligand Therapy (TRT) With Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR Positive (SSTR+) Gastrointestinal (GI) Neuroendocrine Tumors (NET) and Pheochromocytoma/Paragangliomas Previously Treated With Systemic Radioligand Therapy
2 other identifiers
interventional
66
1 country
1
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....
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Feb 2025
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 23, 2024
CompletedFirst Posted
Study publicly available on registry
May 24, 2024
CompletedStudy Start
First participant enrolled
February 7, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2039
March 10, 2026
March 6, 2026
4.4 years
May 23, 2024
March 7, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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).
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
The overall response rate will be presented as a percentage along with 95% confidence intervals. Only evaluable participants will be included.
Baseline until progression or 6 years after receiving the first infusion of study drug.
Secondary Outcomes (5)
Progression Free Survival
Baseline until progression or 10 years after receiving the first infusion of study drug
Safety of [203Pb]VMT-alpha-NET and [212Pb]VMT-alpha-NET
Study duration
Overall Survival
Baseline until progression or 10 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
Dosimetry properties of [212Pb]VMT-alpha-NET via SPECT/CT, using [203Pb]VMT-alpha-NET as a surrogate with and without the administration of amino acids (Dosimetry Arm 1 only)
In Dosimetry Arm 1 after every [203Pb]VMT-alpha-NET infusion
Study Arms (3)
1/Dosimetry Arm 1
EXPERIMENTALEscalating doses of \[212Pb\]VMT-alpha-NET, imaging with \[203Pb\]VMT-alpha-NET.
2/Arm 2
EXPERIMENTALEscalating doses of \[212Pb\]VMT-alpha-NET.
3/Arm 3
EXPERIMENTAL\[212Pb\]VMT-alpha-NET at MTD.
Interventions
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 (6 mCi) will be given IV at 7 days prior.
\[212Pb\]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.
Eligibility Criteria
You may qualify if:
- 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 (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 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
- +15 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Frank I Lin, M.D.
National Cancer Institute (NCI)
Central Study Contacts
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
May 23, 2024
First Posted
May 24, 2024
Study Start
February 7, 2025
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2039
Last Updated
March 10, 2026
Record last verified: 2026-03-06
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.
All IPD recorded in the medical record will be shared with intramural investigators upon request. This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.