[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
NCT Number: NCT06479811
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Head and Neck Tumors|Kidney Cancers|Small Cell Lung Cancers|Pheochromocytoma/Paragangliomas|Gastrointestinal Neuroendocrine Tumors|Somatostatin Receptor Positive
Interventions: DRUG: 68Ga-DOTATATE|DRUG: [203Pb]VMT-alpha-NET|DRUG: [212Pb]VMT-alpha-NET
Sponsor: National Cancer Institute (NCI)
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 120
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-10
Completion Date: 2032-01-01
Locations: National Institutes of Health Clinical Center, Bethesda, Maryland, 20892, United States

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.

Primary Outcome Measures: 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 Outcome Measures: Overall Response Rate, The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The overall response rate will be presented as a percentage along with 95% confidence intervals. Only evaluable participants will be included., 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, PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Kaplan-Meier curves of PFS will be constructed. Median PFS and OS will be reported with 95% confidence intervals., 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, Descriptive tabulations of toxicity will be provided, 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., Study duration|Overall Survival, Kaplan-Meier curves of OS, will be constructed. Median OS will be reported with 95% confidence intervals., 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, PK data will be represented as a scatter plot graphing time vs. the amount of radioactivity found in blood and urine samples., 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), Biodistribution and dosimetry data will be represented in a tabular format which indicates the percentage of the injected dose calculated to be in each of the major organs using gamma scan results. Radiation dose calculations will be performed using OLINDA/EXM software. Absorbed doses in organs and the whole body will be determined using the appropriate adult phantom (e.g., adult male, adult female). Tumor lesion absorbed doses will be determined using the sphere model in OLINDA., After each SPECT/CT and gamma planar imaging and after every [203Pb]VMT-alpha-NET infusion (in Dosimetry Arm 1 only)