Testing the Addition of an Anti-cancer Drug, Triapine, to the Usual Radiation-Based Treatment (Lutetium Lu 177 Dotatate) for Neuroendocrine Tumors

NCT04234568 | Active Not Recruiting Phase 1 Results FDA Drug

• 4 other identifiers: NCI-2020-00170NCI-CIRB-10388-PMC10388UM1CA186712
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 11

Brief Summary

This phase I trial studies the side effects and best dose of triapine when given together with lutetium Lu 177 dotatate in treating patients with neuroendocrine tumors. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as lutetium Lu 177 dotatate, may carry radiation directly to tumor cells and not harm normal cells. Giving triapine and lutetium Lu 177 dotatate together may work better to treat patients with neuroendocrine tumors.

Conditions

Metastatic Neuroendocrine Tumor; Metastatic Digestive System Neuroendocrine Neoplasm

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Triapine and Recommended Phase 2 Dose (RP2D)

  The MTD and RP2D will be estimated using isotonic regression based on observed dose limiting toxicity from all patients enrolled in the phase 1 portion and expansion cohort. All patients who received study drugs will be included in the safety analysis.

  8 weeks (56 days)

• Dose Limiting Toxicity (DLT)

  DLTs will be summarized descriptively at each dose level. Will be summarized based on Common Terminology Criteria for Adverse Events version 5.0. The maximum grade of toxicity for each adverse event category of interest will be recorded for each patient and the summary results will be tabulated by category and grade. Will describe all serious (\>= grade 3) toxicity events on a patient-by-patient basis. Frequency and incidence tables of toxicity and adverse events will be generated in the overall patient group and by dose level depending on patient enrollment.

  8 weeks (56 days)

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  From the start of the treatment until disease progression/recurrence, assessed up to 24 months

• Progression Free Survival (PFS)

  Time from registration to time of progressive disease as defined by Response Evaluation Criteria in Solid Tumors 1.1 criteria or death from any cause, whichever occurs first, assessed up to 24 months

• Overall Survival

  The time from date of enrollment to the date of death due to any cause, assessed up to 24 months

Other Outcomes (5)

• Expression of Somatostatin Receptors

  Up to 24 months

• Whole Exome Sequencing

  Up to 24 months

• Pharmacokinetic (PK) Studies

  Up to 24 months

Study Arms (1)

Treatment (lutetium Lu 177 dotatate, triapine)

EXPERIMENTAL

Patients receive lutetium Lu 177 dotatate IV for 30 to 40 minutes on day 1 of each cycle and triapine PO on days 1 throughout 14 of each cycle. Cycles repeat every 56 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI scan throughout the trial. Patients undergo blood specimen collection on study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Lutetium Lu 177 Dotatate; Procedure: Magnetic Resonance Imaging; Drug: Triapine

Interventions

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (lutetium Lu 177 dotatate, triapine)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (lutetium Lu 177 dotatate, triapine)

Lutetium Lu 177 Dotatate DRUG

Given IV

Also known as: 177 Lu-DOTA-TATE, 177 Lu-DOTA-Tyr3-Octreotate, 177Lu-DOTA0-Tyr3-Octreotate, Lutathera, Lutetium (177Lu) Oxodotreotide, Lutetium Lu 177 DOTA(0)-Tyr(3)-Octreotate, Lutetium Lu 177-DOTA-Tyr3-Octreotate, lutetium Lu 177-DOTATATE, Lutetium Oxodotreotide Lu-177

Treatment (lutetium Lu 177 dotatate, triapine)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (lutetium Lu 177 dotatate, triapine)

Triapine DRUG

Given PO

Also known as: 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191, OCX-191, OCX191, PAN-811

Treatment (lutetium Lu 177 dotatate, triapine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic, histologically confirmed well-differentiated neuroendocrine tumor with positive dotatate scan (gallium-68 or copper-64) within 6 months. Lesions on dotatate scan (gallium-68 or copper-64 dotatate scan) will be considered positive if the maximum standard uptake value (SUVmax) is \> 2 times SUV mean of normal liver parenchyma
• Failure of at least one prior systemic cancer treatment, including somatostatin analogs
• 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
• No prior exposure to peptide receptor radionuclide therapy
• Recovered from adverse events of previously administered therapeutic agents to grade 1 or less toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• Archival tissue no longer than 6 months old should be present, otherwise baseline research biopsy is needed for WES
• 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, but will be eligible for future pediatric trials
• Eastern Cooperative Oncology Group (ECOG) performance status 0,1, or 2 (Karnofsky \>= 60%)
• Leukocytes \>= 2,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelets \>= 75,000/mcL
• Total bilirubin =\< 3 x 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
• Glomerular filtration rate (GFR) \>= 50 mL/min using Cockcroft-Gault method

You may not qualify if:

• Patients who have had major surgical procedures in the prior 6 weeks
• Patients with an inability to swallow oral medications or gastrointestinal disease limiting absorption of oral agents
• Patients who have received prior external beam radiotherapy to more than 50% of bone marrow, as determined by a radiation medicine physicist who will calculate the volume of bone marrow exposure in prior radiotherapy portals divided by the volume of total bone marrow harboring tissues. This ratio must be less than 50 percent
• Uncontrolled congestive heart failure (New York Heart Association \[NYHA\] III, IV)
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) 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 including, but not limited to, ongoing or active infection; symptomatic decompensated congestive heart failure; unstable angina pectoris; cardiac arrhythmia; and known inadequately controlled hypertension
• Patients with psychiatric illness/social situations that would limit compliance with study requirements
• 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
• Discontinue long-acting somatostatin analogs (e.g., long-acting octreotide) for at least 4 weeks prior to initiating lutetium Lu 177 dotatate. Long-acting somatostatin analog will be allowed to continue if patient has history of carcinoid syndrome and requires long-acting somatostatin analog for control of his/her functional syndrome

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

Specimen Handling; lutetium Lu 177 dotatate; Magnetic Resonance Spectroscopy; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Dr. Susanne Arnold
• Organization: University of Kentucky

susanne.arnold@uky.edu

859-323-8043

Study Officials

• Susanne M Arnold

  Ohio State University Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2020
• First Posted: January 21, 2020
• Study Start: July 20, 2020
• Primary Completion: September 17, 2024
• Study Completion (Estimated): March 13, 2027
• Last Updated: April 30, 2026
• Results First Posted: November 3, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (11)