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
National Cancer Institute (NCI)
Summary
Background: Gastrointestinal neuroendocrine tumors (GI NET) are a type of cancer that affects the stomach and intestines; pheochromocytoma/paragangliomas (PPGL) are tumors that grow in or near the adrenal glands. Both of these types of tumor have high levels of a protein called somatostatin receptors (SSTR) on their surfaces. Researchers want to test a treatment that targets SSTR. Objective: To test a drug (\[212Pb\]VMT-alpha-NET) in people with GI NET or PPGL. The drug has 2 components: a protein to bind to SSTR and a radioactive agent to kill the cancer cells. Eligibility: Adults aged 18 years or older with GI NET or PPGL tumors that have spread and cannot be removed with surgery. Design: Participants will be screened. They will have a physical exam, with imaging scans, blood tests, and tests of their heart function. \[212Pb\]VMT-alpha-NET is given through a tube attached to a needle inserted into a vein (infusion). Treatment will be given in four 8 week cycles. Participants will receive the drug on the first day of each cycle. They will remain in the clinic at least 4 hours after each infusion and may need to stay in the hospital for up to 48 hour for monitoring and testing. They will have blood tests every week of 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 for 10 years....
Description
Background: * Somatostatin receptors (SSTR) have been shown to be over-expressed in a number of human tumors, including gastrointestinal (GI) neuroendocrine tumors (NET) and pheochromocytoma/paragangliomas (PPGL). * 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 characterist…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* 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 p…
Interventions
- Drug68Ga-DOTATATE
68Ga-DOTATATE PET/CT whole-body scanning will be done at target dose of 5 mCi. The whole-body PET/CT scan will be started approximately 60 minutes after the tracer injection and will take up to 2 hours.
- Drug[203Pb]VMT-alpha-NET
\[203Pb\]VMT-alpha-NET (6 mCi) will be given IV at 7 days prior.
- Drug[212Pb]VMT-alpha-NET
\[212Pb\]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 Phase II. One cycle is 8 weeks.
Location
- National Institutes of Health Clinical CenterBethesda, Maryland