Health TrialsbyHealthPanel

[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 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.

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

  • 68Ga-DOTATATE

    Drug

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

  • [203Pb]VMT-alpha-NET

    Drug

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

  • [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.

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 3 years (dose expansion).

Secondary outcomes

1

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.

Time frame
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.
2

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.

Time frame
Baseline until progression or 6 years after receiving the first infusion of study drug
3

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
4

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 receiving the first infusion of study drug

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
Apply now