Somatostatin-Receptors (SSTR)-Agonist [212Pb]VMT-alpha-NET in Metastatic or Inoperable SSTR+ Gastrointestinal Neuroendocrine Tumor and Pheochromocytoma/Paraganglioma Previously Treated With Systemic Targeted Radioligand Therapy

Launched by NATIONAL CANCER INSTITUTE (NCI) · May 23, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called \[212Pb\]VMT-alpha-NET for adults with specific types of cancer called gastrointestinal neuroendocrine tumors (GI NET) or pheochromocytomas/paragangliomas (PPGL). These tumors are known to have high levels of a protein called somatostatin receptors on their surfaces, which the new drug targets. The goal of the trial is to see how well this treatment works in patients whose tumors have spread and cannot be surgically removed. To participate, individuals must be at least 18 years old, have confirmed GI NET or PPGL, and have received at least one previous treatment for their cancer.

Participants in the trial will receive the drug through an infusion in a clinic, with treatments scheduled in cycles over several weeks. They will be monitored closely during and after each infusion, including blood tests and scans to track how the drug is working in their body. Follow-up visits will continue for up to 10 years to gather more information. It’s important to note that participants need to meet specific health criteria and agree to safety measures to join the study. This trial offers hope for new treatment options for patients with these challenging cancers.

Gender

ALL

Eligibility 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 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:
• • 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.