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[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

ConditionsSinonasal Neuroendocrine CarcinomaNasopharyngeal CarcinomaEsthesioneuroblastomaOlfactory NeuroblastomaSomatostatin Receptor PositiveSmall Cell Lung CancersPheochromocytoma/ParagangliomasKidney CancersHead and Neck TumorsGastrointestinal Neuroendocrine Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About this trial

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 imaging with a related study drug (\[203Pb\]VMT-Alpha-NET). They will receive this drug within 30 days before each cycle. At 1, 4, 24, and 48 hours after each \[203Pb\]VMT-Alpha-NET infusion and 4 hours after each \[212Pb\]VMT-Alpha-NET infusion, they will have optional whole body scans. These scans will show where the study drug went in their body. Following treatment, participants will be invited to the NIH Clinical Center 8 weeks after the last study drug administration for an end of treatment (EOT) visit. After EOT, visits will continue every 12 weeks for years 1-3 and every 6 months for years 4-6 or until disease progression. Beyond 6 years (or disease progression), participants will be contacted yearly to assess health status for 10 years after EOT.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • [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.

  • [203Pb]VMT-alpha-NET

    Drug

    \[203Pb\]VMT-alpha-NET will be given IV within 30 days prior to each \[212Pb\]VMT-alpha-NET infusion.

  • 68Ga-DOTATATE

    Drug

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

Treatment groups

120 Participants
are divided into 3 treatment groups
Group A: 1/Dosimetry Arm 1Experimental treatment 3 interventions
Group B: 2/Arm 2Experimental treatment 2 interventions
Group C: 3/Arm 3Experimental treatment 2 interventions

Trial outcomes

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.

Time frame
DLTs through 12 weeks after initial 212Pb]VMT-alpha-NET administration (dose escalation) and all toxicities from day 1 up through 6 years (dose expansion).

Secondary outcomes

1

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.

Time frame
After each SPECT/CT and gamma planar imaging and after every [203Pb]VMT-alpha-NET infusion (in Dosimetry Arm 1 only)
2

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.

Time frame
After every infusion of [212Pb]VMT-alpha-NET
3

Overall Survival

Kaplan-Meier curves of OS, will be constructed. Median OS will be reported with 95% confidence intervals.

Time frame
Baseline until progression or 6 years after the end of treatment visit
4

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.

Time frame
Study duration

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov
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