Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

September 1, 2026 updated by: National Cancer Institute (NCI)

A Phase I Trial Combining Triapine With Radiation Therapy for Recurrent Glioblastoma or Astrocytoma

This phase I trial tests the safety, side effects, and best dose of triapine in combination with radiation therapy in treating patients with glioblastoma or astrocytoma that has come back after a period of improvement (recurrent). Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Giving triapine in combination with radiation therapy may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma or astrocytoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To identify the safety and maximally tolerated dose (MTD) of oral triapine used in combination with radiation therapy for patients with recurrent glioblastoma (GBM) or astrocytoma.

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To determine the pharmacokinetics of oral triapine in plasma and the central nervous system (CNS).

III. To evaluate the efficacy of triapine when administered in combination with radiation therapy by assessing:

IIIa. Progression-free survival (PFS); IIIb. Overall survival (OS); IIIc. The proportion of patients requiring bevacizumab for symptom control; IIId. The correlation of genetic mutations in select genes (e.g., p53, p16, KRAS, and Pi3k/mTOR/AKT) with tumor response and clinical outcomes.

OUTLINE: This is a dose-escalation study of triapine in combination with radiation therapy.

Patients undergo intensity-modulated radiation therapy (IMRT) once daily (QD) 5 days per week (Monday-Friday) for a total of 10 treatment days over 2 weeks and receive triapine orally (PO) 2 hours prior to IMRT on each radiation treatment day in the absence of disease progression or unacceptable toxicity. Patients also undergo computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study as well as blood sample collection during screening and on study. Patients may undergo cerebrospinal fluid (CSF) sample collection during screening.

After completion of study treatment, patients are followed up at 2 weeks after radiation therapy, then every 3 months for up to 5 years from study treatment initiation.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope Comprehensive Cancer Center
        • Principal Investigator:
          • Stephanie M. Yoon
        • Contact:
      • Irvine, California, United States, 92612
        • Recruiting
        • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
        • Contact:
        • Principal Investigator:
          • Jerica M. Lomax
      • La Jolla, California, United States, 92093
        • Recruiting
        • UC San Diego Moores Cancer Center
        • Contact:
        • Principal Investigator:
          • David E. Piccioni
      • Orange, California, United States, 92868
        • Recruiting
        • UC Irvine Health/Chao Family Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Jerica M. Lomax
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis Comprehensive Cancer Center
        • Principal Investigator:
          • Orwa Aboud
        • Contact:
          • Site Public Contact
          • Phone Number: 916-734-3089
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Nicholas A. Blondin
      • Trumbull, Connecticut, United States, 06611
        • Recruiting
        • Smilow Cancer Hospital Care Center-Trumbull
        • Contact:
        • Principal Investigator:
          • Nicholas A. Blondin
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Suspended
        • MedStar Georgetown University Hospital
    • Florida
      • Coral Gables, Florida, United States, 33146
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Gables
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • Coral Springs, Florida, United States, 33065
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Coral Springs
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • Deerfield Beach, Florida, United States, 33442
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • Doral, Florida, United States, 33166
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Doral
        • Principal Investigator:
          • Macarena I. De La Fuente
        • Contact:
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Hollywood
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine-Sylvester Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • Miami, Florida, United States, 33176
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Kendall
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
      • North Miami, Florida, United States, 33181
        • Recruiting
        • University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
        • Principal Investigator:
          • Macarena I. De La Fuente
        • Contact:
      • Plantation, Florida, United States, 33324
        • Recruiting
        • UM Sylvester Comprehensive Cancer Center at Plantation
        • Contact:
          • Site Public Contact
          • Phone Number: 305-243-2647
        • Principal Investigator:
          • Macarena I. De La Fuente
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Emory University Hospital/Winship Cancer Institute
        • Principal Investigator:
          • Kimberly Hoang
        • Contact:
          • Site Public Contact
          • Phone Number: 404-778-1868
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Lauren Singer
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Karan Dixit
      • Shiloh, Illinois, United States, 62269
        • Active, not recruiting
        • Memorial Hospital East
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Clinical Research Center
        • Contact:
        • Principal Investigator:
          • Tolga Tuncer
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
        • Principal Investigator:
          • Tolga Tuncer
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Contact:
        • Principal Investigator:
          • Tolga Tuncer
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • University of Kentucky/Markey Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 859-257-3379
        • Principal Investigator:
          • John L. Villano
    • Missouri
      • City of Saint Peters, Missouri, United States, 63376
        • Active, not recruiting
        • Siteman Cancer Center at Saint Peters Hospital
      • Creve Coeur, Missouri, United States, 63141
        • Active, not recruiting
        • Siteman Cancer Center at West County Hospital
      • St Louis, Missouri, United States, 63110
        • Active, not recruiting
        • Washington University School of Medicine
      • St Louis, Missouri, United States, 63129
        • Active, not recruiting
        • Siteman Cancer Center-South County
      • St Louis, Missouri, United States, 63136
        • Active, not recruiting
        • Siteman Cancer Center at Christian Hospital
    • New York
      • Mineola, New York, United States, 11501
        • Recruiting
        • NYU Langone Hospital - Long Island
        • Principal Investigator:
          • Marissa Barbaro
        • Contact:
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Peter C. Pan
      • New York, New York, United States, 10016
        • Recruiting
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
        • Principal Investigator:
          • Marissa Barbaro
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Recruiting
        • Carolinas Medical Center/Levine Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 800-804-9376
        • Principal Investigator:
          • Ashley L. Sumrall
      • Winston-Salem, North Carolina, United States, 27157
        • Recruiting
        • Wake Forest University Health Sciences
        • Contact:
          • Site Public Contact
          • Phone Number: 336-713-6771
        • Principal Investigator:
          • Roy E. Strowd
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Hamid R. Mohtashami
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • James D. Battiste
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • UPMC Hillman Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
        • Principal Investigator:
          • Megan Mantica
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University/Ingram Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-811-8480
        • Principal Investigator:
          • Alexander C. Mohler
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute/University of Utah
        • Contact:
        • Principal Investigator:
          • Joe S. Mendez
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Suspended
        • VCU Massey Comprehensive Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - University Hospital
        • Contact:
        • Principal Investigator:
          • Brett A. Morris
      • Madison, Wisconsin, United States, 53718
        • Recruiting
        • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
        • Contact:
        • Principal Investigator:
          • Brett A. Morris

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients must have histologically, molecularly, or cytologically confirmed recurrent astrocytic tumors including:

    • GBM or variants, IDH-wildtype, grade 2-4 (standard curative measures available or not)
    • Astrocytoma, IDH-mutant, grade 2-4 (standard curative measures available or not)
    • Diffuse midline gliomas, including pediatric-type H3 G34 or E3 K27 mutant tumors.

  • Tumors ≤ 6 cm in maximal diameter.

    • Patients who had recent resection for recurrent tumor must have measurable disease.
  • Patients must have at least a 6-month break from last dose of radiation therapy.

Re-irradiation within 6 months may increase risk for radiation necrosis/edema, which will affect toxicity assessment and patient safety. Additionally, GBM and other high-grade astrocytic tumors can exhibit pseudo-progression within 6 months from completing definitive, 1st line radiation therapy, and re-irradiation during this period will increase risk for misattribution of effect.

  • Prior history of standard dose radiation for gliomas of 59.4-60 gray (Gy) in 1.8-2 Gy per fraction (or equivalent or lower) is allowed.

  • Patients who received non-standard radiation dose regimen (e.g., 40 Gy, 34-35 Gy, 25 Gy) or stereotactic radiosurgery are eligible as long as there is at least one of the following:

    • A new tumor outside the original radiotherapy field as determined by the investigator.
    • There is histologic confirmation of tumor on biopsy or resection.
    • Imaging findings are consistent with true progressive disease (on standard MRI sequences, MRI spectroscopy/perfusion, or nuclear medicine imaging).
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of triapine 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.
  • Hemoglobin ≥ 8 g/dL.
  • Platelets ≥ 100,000/mcL.
  • Total bilirubin ≤ 1.5 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.
  • Creatinine ≤ 1.5 x ULN OR glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m^2.
  • 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 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 II or better.
  • Patients must be able to swallow whole capsules.
  • Patients must be able to undergo MRIs with contrast. Patients with non-compatible devices with MRI can be eligible if CT scans of sufficient quality are obtained. However, patients without non-compatible devices may not use CT scans to meet this requirement.
  • The effects of triapine on the developing human fetus are unknown. For this reason and because ribonucleotide reductase (RNR) inhibitor agent and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 12 months after finishing study treatment. People of child-bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 2 weeks of registration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 12 months after completion of triapine administration.
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

  • 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.
  • Patients who are actively taking medications that are known to induce methemoglobinemia (e.g. sulfonamides, nitrofurans, anti-malarials [primaquine, chloroquine], cyclophosphamide, and ifosfamide).
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine.
  • Patients with known G6PD deficiency. Testing for G6PD deficiency is not required.
  • Patients with uncontrolled intercurrent illness, active infections, or any other significant condition(s) that would make participation in this protocol unreasonably hazardous.
  • Pregnant women are excluded from this study because triapine is a RNR inhibitor agent 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, breastfeeding should be discontinued if the mother is treated with triapine. These potential risks may also apply to the radiation used in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (IMRT, triapine)
Patients undergo IMRT QD 5 days per week (Monday-Friday) for a total of 10 treatment days over 2 weeks and receive triapine PO 2 hours prior to IMRT on each radiation treatment day in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or MRI throughout the study as well as blood sample collection during screening and on study. Patients may undergo CSF sample collection during screening.
Procedure: Magnetic Resonance Imaging
Undergo MRI
Other Names:
  • MRI
  • Magnetic Resonance
  • Magnetic Resonance Imaging Scan
  • Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  • MR
  • MR Imaging
  • MRI Scan
  • NMR Imaging
  • NMRI
  • Nuclear Magnetic Resonance Imaging
  • Magnetic Resonance Imaging (MRI)
  • sMRI
  • Magnetic resonance imaging (procedure)
  • MRIs
  • Structural MRI
Procedure: Computed Tomography
Undergo CT
Other Names:
  • CT
  • CAT
  • CAT Scan
  • Computed Axial Tomography
  • Computerized Axial Tomography
  • Computerized Tomography
  • CT Scan
  • tomography
  • Computerized axial tomography (procedure)
  • Computerized Tomography (CT) scan
  • Diagnostic CAT Scan
  • Diagnostic CAT Scan Service Type
Radiation: Intensity-Modulated Radiation Therapy
Undergo IMRT
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
  • Radiation, Intensity-Modulated Radiotherapy
  • Intensity modulated radiation therapy (procedure)
Drug: Triapine
Given PO
Other Names:
  • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
  • 3-AP
  • 3-Apct
  • OCX-0191
  • OCX-191
  • OCX191
  • PAN-811
Procedure: Biospecimen Collection
Undergo blood and CSF sample collection
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
  • Sample Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicity
Time Frame: Up to 28 days
Will be graded in severity according to the Common Terminology Criteria for Adverse Events version 5.0. Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized with descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient and frequency tables will be reviewed to determine toxicity patterns. Will employ the Backfill Bayesian Optimal Interval design to guide dose escalation and establish the maximal tolerated dose (MTD). The target toxicity rate for the MTD is = 0.25.
Up to 28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma pharmacokinetic (PK) parameters
Time Frame: Up to 2 weeks
Triapine in plasma and peri-tumoral dialysate will be quantified using a validated liquid chromatography-tandem mass spectrometry assay. Plasma PK parameters will be derived and compared to historical controls. Dialysate concentrations will be calculated at multiple time points. Exploratorily, exposure-response relationships will be evaluated.
Up to 2 weeks
Response rate
Time Frame: Up to 5 years
Response rate will be categorized based on the Response Assessment in Neuro-Oncology criteria, in which tumor response is based on clinical history, physical exam, and imaging findings. The total number of patients in each response category divided by the total number of evaluable patients determines response rate. An evaluable patient is defined as an eligible patient who received at least one dose of triapine. The response rates will be calculated with corresponding 95% exact Clopper-Pearson confidence intervals.
Up to 5 years
Progression-free survival
Time Frame: From study enrollment to date of either disease progression or death, assessed up to 5 years
Will be estimated using Kaplan Meier curves.
From study enrollment to date of either disease progression or death, assessed up to 5 years
Overall survival
Time Frame: From study enrollment to date of death, assessed up to 5 years
Will be estimated using Kaplan Meier curves.
From study enrollment to date of death, assessed up to 5 years
Proportion of patients who initiated bevacizumab for symptom control
Time Frame: Up to 5 years
Will be calculated using descriptive statistics.
Up to 5 years
Tumor tissue biomarkers
Time Frame: Up to 5 years
The presence of genetic alterations, expression of RRM2, and other molecular gene expression signatures will be descriptive in relation to tumor response and clinical outcomes.
Up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Stephanie M Yoon, City of Hope Comprehensive Cancer Center LAO

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 30, 2025

Primary Completion (Estimated)

June 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

March 5, 2025

First Submitted That Met QC Criteria

March 5, 2025

First Posted (Actual)

March 6, 2025

Study Record Updates

Last Update Posted (Actual)

September 2, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2025-01531 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UM1CA186717 (U.S. NIH Grant/Contract)
  • 10699 (Other Identifier: CTEP)
  • PHI-151

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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