Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06427798
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-05-23
Brief Title:
Somatostatin-Receptors SSTR-Agonist 212PbVMT-alpha-NET in Metastatic or Inoperable SSTR Gastrointestinal Neuroendocrine Tumor and PheochromocytomaParaganglioma Previously Treated With Systemic Targeted Radioligand Therapy
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase III Trial of Systemic Targeted Radioligand Therapy TRT With Somatostatin-Receptors SSTR-Agonist 212PbVMT-alpha-NET in Metastatic or Inoperable SSTR Positive SSTR Gastrointestinal GI Neuroendocrine Tumors NET and PheochromocytomaParagangliomas Previously Treated With Systemic Radioligand Therapy
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Gastrointestinal neuroendocrine tumors GI NET are a type of cancer that affects the stomach and intestines pheochromocytomaparagangliomas 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 212PbVMT-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
212PbVMT-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 nee to stay in th 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 203PbVMT-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
Gastrointestinal neuroendocrine tumors GI NET are a type of cancer that affects the stomach and intestines pheochromocytomaparagangliomas 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 212PbVMT-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
212PbVMT-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 nee to stay in th 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 203PbVMT-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
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 and pheochromocytomaparagangliomas 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 characteristics of the ligand-receptortransporter pair
While there have been clinical successes with treating gastrointestinal neuroendocrine tumors GI NET and PPGL with SSTR-targeting beta-emitting TRTs tumors will invariably start to progress after some time Re-treatment using the same beta-emitting agents at the time of progression can be done but has decreased efficacy compared to the TRT-naive setting
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 and could be better than betas in the re-treatment setting
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
203PbVMT-alpha-NET is the chemically identical imaging surrogate for 212PbVMT-alpha-NET and has the same mechanism of action via binding to SSTR2 The nuclide 203Pb contained in 203PbVMT-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
Objectives
Phase I To determine the maximal tolerated dose MTD of 212PbVMT-alpha-NET using a 33 dose escalation design in GI NET and PPGL in a re-treatment setting
Phase II To determine the Overall Response Rate ORR by Response Evaluation Criteria in Solid Tumors RECIST 11 of participants treated with 212PbVMT-alpha-NET at the MTD at the completion of 4 cycles of treatment reported by disease groups
Eligibility
Age 18 years
Histopathologically confirmed GI NET or PPGL that are metastatic or inoperable
At least 1 prior systemic radioligand therapy
Eastern Cooperative Oncology Group ECOG Performance Status 1
Design
This is an open-label single-arm single-center phase III study evaluating the safety preliminary efficacy and pharmacokinetic properties of 212PbVMT-alpha-NET in GI NET and PPGL in a re-treatment setting
Phase I participants will be accrued using a 33 dose escalation design with 3 dose levels to estimate MTD of 212PbVMT-alpha-NET Once MTD is estimated Phase II participants with GI NET and PPGL will be accrued in separate cohorts and treated at MTD of 212PbVMT-alpha-NET
212PbVMT-alpha-NET will be given IV every 8 weeks for a total of 4 administrations
A subset of participants Dosimetry Arm 1 will have 203PbVMT-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 212PbVMT-alpha-NET Cycles 1-2
All participants will undergo serial whole-body dose rate measurements after 203PbVMT-alpha-NET andor 212PbVMT-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 years 1-3 every 6 months for years 4-6 for safety and efficacy assessments Beyond 6 years participants will be contacted annually through any NIH-approved platform to assess for overall survival and health status
Somatostatin receptors SSTR have been shown to be over-expressed in a number of human tumors including gastrointestinal GI neuroendocrine tumors NET and pheochromocytomaparagangliomas 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 characteristics of the ligand-receptortransporter pair
While there have been clinical successes with treating gastrointestinal neuroendocrine tumors GI NET and PPGL with SSTR-targeting beta-emitting TRTs tumors will invariably start to progress after some time Re-treatment using the same beta-emitting agents at the time of progression can be done but has decreased efficacy compared to the TRT-naive setting
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 and could be better than betas in the re-treatment setting
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
203PbVMT-alpha-NET is the chemically identical imaging surrogate for 212PbVMT-alpha-NET and has the same mechanism of action via binding to SSTR2 The nuclide 203Pb contained in 203PbVMT-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
Objectives
Phase I To determine the maximal tolerated dose MTD of 212PbVMT-alpha-NET using a 33 dose escalation design in GI NET and PPGL in a re-treatment setting
Phase II To determine the Overall Response Rate ORR by Response Evaluation Criteria in Solid Tumors RECIST 11 of participants treated with 212PbVMT-alpha-NET at the MTD at the completion of 4 cycles of treatment reported by disease groups
Eligibility
Age 18 years
Histopathologically confirmed GI NET or PPGL that are metastatic or inoperable
At least 1 prior systemic radioligand therapy
Eastern Cooperative Oncology Group ECOG Performance Status 1
Design
This is an open-label single-arm single-center phase III study evaluating the safety preliminary efficacy and pharmacokinetic properties of 212PbVMT-alpha-NET in GI NET and PPGL in a re-treatment setting
Phase I participants will be accrued using a 33 dose escalation design with 3 dose levels to estimate MTD of 212PbVMT-alpha-NET Once MTD is estimated Phase II participants with GI NET and PPGL will be accrued in separate cohorts and treated at MTD of 212PbVMT-alpha-NET
212PbVMT-alpha-NET will be given IV every 8 weeks for a total of 4 administrations
A subset of participants Dosimetry Arm 1 will have 203PbVMT-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 212PbVMT-alpha-NET Cycles 1-2
All participants will undergo serial whole-body dose rate measurements after 203PbVMT-alpha-NET andor 212PbVMT-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 years 1-3 every 6 months for years 4-6 for safety and efficacy assessments Beyond 6 years participants will be contacted annually through any NIH-approved platform to assess for overall survival and health status
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001711-C | None | None | None |