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
A Phase II Randomized Control Trial of Triapine Plus Lutetium Lu 177 Dotatate Versus Lutetium Lu 177 Dotatate Alone for Well-Differentiated Somatostatin Receptor-Positive Neuroendocrine Tumors
4 other identifiers
interventional
94
1 country
25
Brief Summary
This phase II trial compares the effect of adding triapine to lutetium Lu 177 dotatate versus lutetium Lu 177 dotatate alone (standard therapy) in shrinking tumors or slowing tumor growth in patients with neuroendocrine tumors that have spread from where they first started (primary site) to other places in the body (metastatic). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for deoxyribonucleic acid synthesis and cell growth. Lutetium Lu 177 dotatate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177 dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Giving triapine in combination with lutetium Lu 177 dotatate may be more effective at shrinking tumors or slowing tumor growth in patients with metastatic neuroendocrine tumors than the standard therapy of lutetium Lu 177 dotatate alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Aug 2023
Typical duration for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 10, 2023
CompletedFirst Posted
Study publicly available on registry
February 13, 2023
CompletedStudy Start
First participant enrolled
August 30, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 9, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 9, 2026
April 13, 2026
January 1, 2026
3.3 years
February 10, 2023
April 9, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall response rate
Estimated along with exact 95% binomial confidence intervals in each arm and compared between arms using the z-test statistic.
Up to 5 years
Secondary Outcomes (1)
Progression free survival (PFS)
Time from the date of randomization to the date of first documented progression or death due to any cause, assessed up to 5 years
Other Outcomes (8)
Plasma hPG80
Up to 5 years
Plasma deoxyribonucleosides
Pre- to post-triapine administration
Circulating deoxyribonucleic acid (ctDNA)
Up to 5 years
- +5 more other outcomes
Study Arms (2)
Arm 1 (triapine, lutetium Lu 177 dotatate)
EXPERIMENTALPatients 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.
Arm 2 (lutetium Lu 177 dotatate)
ACTIVE COMPARATORPatients 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.
Interventions
Given IV
Undergo MRI
Given PO
Undergo collection of blood samples
Undergo CT
Eligibility Criteria
You may qualify if:
- Patients must have metastatic, histologically confirmed well-differentiated neuroendocrine tumor with positive gallium 68 DOTATATE or copper 64 DOTATATE scan. Lesions on dotatate scan will be considered positive if the standardized uptake value maximum (SUVmax) of target lesion is \> 2 times standardized uptake value (SUV) mean of normal liver parenchyma. Patients with lung neuroendocrine tumors (NETs) are excluded from the trial
- 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)
- +8 more criteria
You may not qualify if:
- Patients who have not recovered from adverse events of previously administered therapeutic agents (i.e., have residual toxicities \> grade 2) according to CTCAE 5.0, with the exception of alopecia
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (25)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
MD Anderson in The Woodlands
Conroe, Texas, 77384, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MD Anderson West Houston
Houston, Texas, 77079, United States
MD Anderson League City
League City, Texas, 77573, United States
MD Anderson in Sugar Land
Sugar Land, Texas, 77478, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lowell B Anthony
Ohio State University Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 10, 2023
First Posted
February 13, 2023
Study Start
August 30, 2023
Primary Completion (Estimated)
December 9, 2026
Study Completion (Estimated)
December 9, 2026
Last Updated
April 13, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.