This study is NOT currently recruiting participants.
Number
001711-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Recruitment has not started Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Children;Neonates;Fetuses
Keywords
212Pb; Targeted Therapy; Image-Guided Dosimetry; VMT- -NET
Recruitment Keyword(s)
None
Condition(s)
Somatostatin Receptor Positive; Gastrointestinal Neuroendocrine Tumors; Pheochromocytoma; Paragangliomas
Investigational Drug(s)
[203Pb]VMT-alpha-NET [212Pb]VMT-alpha-NET
Investigational Device(s)
Intervention(s)
Drug: 68Ga-DOTATATE Drug: [203Pb]VMT-alpha-NET Drug: [212Pb]VMT-alpha-NET
Supporting Site
National Cancer Institute
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 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 ([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.
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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% 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. -Women of child-bearing potential (WOCBP) and men 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). -Breastfeeding participants must be willing to discontinue breastfeeding 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 females of childbearing potential 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.
-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% 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.
-Women of child-bearing potential (WOCBP) and men 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).
-Breastfeeding participants must be willing to discontinue breastfeeding 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 females of childbearing potential 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.
Principal Investigator
Referral Contact
For more information: