Testing the Effectiveness of an Anti-cancer Drug, Triapine, When Used With Targeted Radiation-based Treatment (Lutetium Lu 177 Dotatate), Compared to Lutetium Lu 177 Dotatate Alone for Metastatic Neuroendocrine Tumors
NCT ID: NCT05724108
Last Updated: 2025-11-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
94 participants
INTERVENTIONAL
2023-08-30
2025-11-30
Brief Summary
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Detailed Description
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I. Evaluate the overall response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of combination triapine + lutetium Lu 177 dotatate (treatment arm 1) versus standard of care lutetium Lu 177 dotatate alone (treatment arm 2).
SECONDARY OBJECTIVE:
I. Evaluate progression-free survival (PFS) between the two treatment arms (combination arm 1 versus standard of care arm 2).
EXPLORATORY OBJECTIVES:
I. Evaluate plasma hPG80 as a biomarker of treatment response. II. Evaluate plasma deoxyribonucleosides as a biomarker of triapine resistance. III. Collect plasma for circulating deoxyribonucleic acid (DNA) (ctDNA) assessment.
IV. Evaluate triapine plasma pharmacokinetics (PK) in the combination arm (treatment arm 1 only).
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1: Patients receive triapine orally (PO) once daily (QD) on days 1-14 of each cycle and lutetium Lu 177 dotatate intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial.
ARM 2: Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up at 8 and 12 months, then every 6 months for 2 years.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm 1 (triapine, lutetium Lu 177 dotatate)
Patients receive triapine PO QD on days 1-14 of each cycle and lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT
Lutetium Lu 177 Dotatate
Given IV
Magnetic Resonance Imaging
Undergo MRI
Triapine
Given PO
Arm 2 (lutetium Lu 177 dotatate)
Patients receive lutetium Lu 177 dotatate IV over 30 minutes on day 1 of each cycle. Cycles repeat every 8 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI and collection of blood samples throughout the trial.
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT
Lutetium Lu 177 Dotatate
Given IV
Magnetic Resonance Imaging
Undergo MRI
Interventions
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Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT
Lutetium Lu 177 Dotatate
Given IV
Magnetic Resonance Imaging
Undergo MRI
Triapine
Given PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Patients must have progressive disease based on RECIST criteria, version 1.1 evidenced with CT scans/MRI obtained within 24 months from enrollment
* Patients must have measurable disease per RECIST 1.1
* Failure of at least one prior systemic cancer treatment with somatostatin analogs
* No prior exposure to peptide receptor radionuclide therapy
* Recovered from adverse events of previously administered therapeutic agents (i.e., to grade 2 or less toxicity) according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0
* Age \>= 18 years
* Because no dosing or adverse event data are currently available on the use of triapine in combination with lutetium Lu 177 dotatate in patients \< 18 years of age, children are excluded from this study
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1,500/mcL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN
* Serum creatinine =\< 1.5 institutional ULN. Creatinine \> 1.5 ULN will require a measured creatinine clearance (CrCl) \> 50 ml/min to qualify
* Hemoglobin \> 5.0 mmol/L (\> 8.0 g/dL)
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases and off steroids are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 4 weeks prior to enrollment in the study. Patients with a history of brain metastases must have a head CT with contrast to document stable disease prior to enrollment in the study
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Pregnancy precaution: Men and women should avoid pregnancy for seven months after the date of their last treatment with lutetium Lu 177 dotatate. It is noteworthy that beta-human chorionic gonadotropin (beta-HCG) may be secreted by a small percentage of NETs, such that, in addition to being a pregnancy marker, it also is a tumor marker. Consequently, NET female patients with positive beta-HCG (\> 5 mIU/mL) at baseline can be eligible to enter the study and receive treatment if pregnancy can be excluded by lack of expected doubling of beta-HCG and negative pelvic ultrasound. Normally, in pregnant subjects beta-HCG doubles every 2 days during the first 4 weeks of pregnancy and every 3.5 days by weeks 6 to 7. Women of childbearing potential include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral ovariectomy) or is not postmenopausal (defined as amenorrhea \> 12 consecutive months, and for women on hormone replacement therapy, only with a documented plasma follicle-stimulating hormone \[FSH\] level \> 35 mIU/mL). Even women who are using oral, implanted, or injected contraceptive hormones, an intrauterine device (IUD), or barrier methods (diaphragm, condoms, spermicidal) to prevent pregnancy, are practicing abstinence or where the partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential. Postmenopausal women who have fertilized eggs implanted are also considered to be of childbearing potential. Acceptable methods of contraception may include total abstinence at the discretion of the Investigator in cases where the age, career, lifestyle, or sexual orientation of the patient ensures compliance. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception (hormonal or barrier method of birth control; abstinence) should be maintained throughout the study and for 7 months after study treatment discontinuation. All men and women of childbearing potential and male partners must use a double-barrier method of birth control or practice continuous abstinence from heterosexual contact throughout the study and for seven months after the end of the last treatment
* Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
* Patients who are receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or lutetium Lu 177 dotatate
* Patients with uncontrolled intercurrent illness
* Uncontrolled congestive heart failure (New York Heart Association \[NYHA\] III, IV)
* Pregnant women are excluded from this study because triapine is a ribonucleotide reductase (RNR) inhibitor and lutetium Lu 177 dotatate is a peptide receptor radionuclide therapy with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with triapine and lutetium Lu 177 dotatate, breastfeeding should be discontinued if the mother is treated with triapine and lutetium Lu 177 dotatate and for 2.5 months following the last treatment
* Inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
* Patients with any other significant condition, currently uncontrolled by treatment, which may interfere with completion of the study
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Lowell B Anthony
Role: PRINCIPAL_INVESTIGATOR
Ohio State University Comprehensive Cancer Center LAO
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
NYP/Weill Cornell Medical Center
New York, New York, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
MD Anderson in The Woodlands
Conroe, Texas, United States
M D Anderson Cancer Center
Houston, Texas, United States
MD Anderson West Houston
Houston, Texas, United States
MD Anderson League City
League City, Texas, United States
MD Anderson in Sugar Land
Sugar Land, Texas, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2023-01224
Identifier Type: REGISTRY
Identifier Source: secondary_id
NCI-CIRB-10558-PMC
Identifier Type: -
Identifier Source: secondary_id
10558
Identifier Type: OTHER
Identifier Source: secondary_id
10558
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2023-01224
Identifier Type: -
Identifier Source: org_study_id