Background:
- Somatostatin receptors (SSTR) have been shown to be over-expressed in a number of
human tumors, including gastrointestinal (GI) neuroendocrine tumors (NET),
pheochromocytoma/paragangliomas (PPGL), small cell lung cancers (SCLC), kidney
cancers (KC), and some head and neck (H&N) cancers.
- Targeted radioligand therapy (TRT) is a class of cancer therapeutic agents formed by
attaching a radioactive isotope to a ligand that can target specific surface
receptors such as SSTR on a tumor cell membrane. Efficacy is typically determined by
the radiation dose deposited onto a tumor, which is determined by the radioactive
isotope being used as well as the binding characteristics of the
ligand-receptor/transporter pair.
- Alpha emitters such as 212Pb emit alpha particles that are more damaging to tumor
cells than beta emitters such as 177Lu. Therefore, TRT agents using alpha emitters
are considered to be more potent than beta-emitting TRTs.
- VMT-Alpha-NET is a peptide that binds to SSTR, which when attached to 212Pb becomes
an alpha particle-emitting TRT that can be used to treat tumors that have SSTR
surface expression.
- [203Pb]VMT-Alpha-NET is the chemically identical imaging surrogate for
[212Pb]VMT-Alpha-NET and has the same mechanism of action via binding to SSTR2. The
nuclide 203Pb contained in [203Pb]VMT-Alpha-NET emits gamma radiation suitable for
single-photon emission computerized tomography (SPECT) imaging. These images can be
used to assess drug product biodistribution throughout the body.
Objective:
-To determine the maximum tolerated dose (MTD) of [212Pb]VMT-Alpha-NET (dose escalation
cohort) and assess the safety of [212Pb]VMT-Alpha-NET at the MTD (dose expansions
cohorts).
Eligibility:
- Age >= 18 years.
- Histopathologically confirmed GI NET, PPGL, SCLC, KC, or H&N (nasopharyngeal
carcinoma [NPC], olfactory neuroblastoma [ONB], sinonasal neuroendocrine carcinoma
[SNEC]) cancers that are metastatic or inoperable.
- No prior systemic radioligand therapy.
- Eastern Cooperative Oncology Group (ECOG) Performance Status <= 1.
Design:
- This is an open-label, single-arm, single-center, phase I study evaluating the
safety, preliminary efficacy, and pharmacokinetic properties of [212Pb]VMT-Alpha-NET
in GI NET, PPGL, SCLC, KC, or H&N cancers.
- First, participants will be accrued in Dose Escalation Part with 4 dose levels to
estimate MTD of [212Pb]VMT-Alpha-NET. Once MTD is estimated, the following
participants with GI NET, PPGL, SCLC, KC, or H&N cancers will be accrued in separate
cohorts and treated at MTD of [212Pb]VMT-Alpha-NET.
- [212Pb]VMT-Alpha-NET will be given IV every 8 weeks for a total of 4
administrations.
- A subset of participants (Dosimetry Arm 1) will have [203Pb]VMT-Alpha-NET
administration followed by whole-body gamma scans combined with dosimetry SPECT/
Computed Tomography (CT) scans and collection of blood and urine samples prior to
the first and the second doses of [212Pb]VMT-Alpha-NET (Cycles 1-2).
- All participants will undergo serial whole-body dose rate measurements after
[203Pb]VMT-Alpha-NET and/or [212Pb]VMT-Alpha-NET administration.
- Participants will have timed clinical laboratory evaluations, imaging studies, and
research blood, and urine samples while on the study therapy for safety and efficacy
evaluations.
- Following completion of treatment, participants will be seen at the NIH Clinical
Center approximately 30 days later, every 12 weeks for 3 years after that for safety
and efficacy assessments. Beyond 3 years, participants will be contacted annually
through any NIH-approved platform to assess for overall survival and health status.