Targeted treatment for advanced gastrointestinal neuroendocrine tumors and pheochromocytoma
Phase I/II Trial of Systemic Targeted Radioligand Therapy (TRT) With Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR Positive (SSTR+) Gastrointestinal (GI) Neuroendocrine Tumors (NET) and Pheochromocytoma/Paragangliomas Previously Treated With Systemic Radioligand Therapy
This study is testing a new drug to see if it can help people with advanced gastrointestinal neuroendocrine tumors and pheochromocytoma who have already tried other treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 66 (estimated) |
| Ages | 18 Years to 120 Years |
| Sex | All |
| Sponsor | National Institutes of Health Clinical Center (CC) NIH |
| Drugs / interventions | radiation |
| Locations | 1 site (Bethesda, Maryland) |
| Trial ID | NCT06427798 on ClinicalTrials.gov |
What this trial studies
This clinical trial aims to evaluate the efficacy of a novel drug, [212Pb]VMT-alpha-NET, which targets somatostatin receptors in patients with metastatic or inoperable gastrointestinal neuroendocrine tumors (GI NET) and pheochromocytoma/paraganglioma (PPGL). The treatment involves administering the drug through an infusion over four cycles of eight weeks each. Participants will undergo screening that includes physical exams, imaging scans, blood tests, and heart function assessments to determine eligibility. The study focuses on patients who have previously received systemic targeted radioligand therapy and have measurable disease progression.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 years or older with confirmed metastatic or inoperable GI NET or PPGL who have previously undergone systemic radioligand therapy.
Not a fit: Patients with tumors that do not express somatostatin receptors or those who have not received prior systemic targeted therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced neuroendocrine tumors that have not responded to previous therapies.
How similar studies have performed: Previous studies have shown success with beta-emitting targeted radioligand therapies, but the use of alpha emitters like [212Pb] is a novel approach that has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
* INCLUSION CRITERIA: * Participants must have histopathologically confirmed gastrointestinal neuroendocrine tumors (GI NET) or pheochromocytoma/paraganglioma (PPGL) cancers that are metastatic or inoperable per Standard of Care. * Have received at least 1 prior systemic radioligand therapy for definitive therapeutic purposes. Note: Participants with prior external beam radiation treatment (EBRT) will also be eligible as long as they have had at least 1 prior administration of a systemic radioligand therapy. * Must have at least 1 measurable lesion by RECIST 1.1 (phase II only). * History of 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 percent 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/miroliter * 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. * Participants may enroll in this study while on another therapeutic trial in order to start the screening process. However, all other investigational agents should be stopped at least 28 days prior to receiving \[203Pb\]VMT-alpha-NET. * 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 at least 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: * 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 i 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.
Where this trial is running
Bethesda, Maryland
- National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
Study contacts
- Principal investigator: Frank I Lin, M.D. — National Cancer Institute (NCI)
- Study coordinator: Joy H Zou, R.N.
- Email: joy.zou@nih.gov
- Phone: (240) 760-6153
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.