Trial Title:
[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 ID:
NCT06479811
Condition:
Head and Neck Tumors
Kidney Cancers
Small Cell Lung Cancers
Pheochromocytoma/Paragangliomas
Gastrointestinal Neuroendocrine Tumors
Somatostatin Receptor Positive
Conditions: Official terms:
Neoplasms
Head and Neck Neoplasms
Small Cell Lung Carcinoma
Neuroendocrine Tumors
Pheochromocytoma
Paraganglioma
Intestinal Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Conditions: Keywords:
212Pb
Targeted alpha Therapy
Image-Guided Dosimetry
VMT-alpha-NET
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
68Ga-DOTATATE
Description:
68Ga-DOTATATE PET/CT whole-body scanning will be done at at different intervals to
monitor disease.
Arm group label:
1/Dosimetry Arm 1
Arm group label:
2/Arm 2
Arm group label:
3/Arm 3
Intervention type:
Drug
Intervention name:
[203Pb]VMT-alpha-NET
Description:
[203Pb]VMT-alpha-NET will be given IV 7 days prior to [212Pb]VMT-alpha-NET.
Arm group label:
1/Dosimetry Arm 1
Intervention type:
Drug
Intervention name:
[212Pb]VMT-alpha-NET
Description:
[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.
Arm group label:
1/Dosimetry Arm 1
Arm group label:
2/Arm 2
Arm group label:
3/Arm 3
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
- INCLUSION CRITERIA:
- 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.
- Required prior therapies:
- 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.
- Have NOT received prior systemic radioligand therapy for definitive therapeutic
purposes. Prior external beam radiation therapy is allowed.
- History of disease 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% 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/microliter
- 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
- Creatinine: within normal institutional limits
OR
- Calculated creatinine clearance (glomerular filtration rate (eGFR): >= 60
mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
- Participants with treated brain metastases are eligible if follow-up brain
imaging after central nervous system (CNS)-directed therapy shows no evidence
of progression at screening.
- Participants with new or progressive brain metastases or leptomeningeal disease
are eligible as long as the participant is asymptomatic and not requiring
medication for symptom control from the brain lesions at screening.
- Participants seropositive for human immunodeficiency virus (HIV) must:
- be on effective anti-retroviral therapy; and
- have an undetectable viral load at screening.
- Participants seropositive for hepatitis B virus (HBV), must have HBV viral load
undetectable at screening.
- Participants seropositive for hepatitis C virus (HCV) must:
- received curative treatment; and
- have an undetectable HCV viral load at screening.
- Individuals of child-bearing potential (IOCBP) and individuals who can father
children must agree to use an effective method of contraception (barrier,
hormonal, intrauterine device [IUD], surgical sterilization, abstinence) at
study entry and up to 6 months after the last dose of the study agent(s).
- Nursing participants must be willing to discontinue nursing from study
treatment initiation through 6 months after the last dose of the study agents.
- The ability of the participant to understand and the willingness to sign a
written informed consent document.
EXCLUSION CRITERIA:
- 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.
- Positive Beta human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test
performed in 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
120 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Contact:
Last name:
National Cancer Institute Referral Office
Phone:
888-624-1937
Email:
ncimo_referrals@mail.nih.gov
Start date:
November 17, 2024
Completion date:
January 1, 2032
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Institutes of Health Clinical Center (CC)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06479811
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001709-C.html
