Astrocytoma, IDH-Mutant, Grade 2Phase 1NCT06860594
Testing the Addition of an Anti-Cancer Drug, Triapine, to the Usual Radiation Therapy for Recurrent Glioblastoma or Astrocytoma
A Phase 1 study testing Biospecimen Collection, Computed Tomography and Intensity-Modulated Radiation Therapy in people with Astrocytoma, IDH-Mutant, Grade 2 and Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant, run by National Cancer Institute (NCI) at 43 sites in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Astrocytoma, IDH-Mutant, Grade 2, Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Adult Diffuse Midline Glioma, H3 K27-Mutant
- What is being tested?
- Biospecimen Collection, Computed Tomography and Intensity-Modulated Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 43 sitesUnited States
- Study dates
- 30 Jul 2025to 30 Jun 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
43 sites in 1 country. Contact the study team or a site near you to ask about taking part.
43 sites in 1 country
United States43 sites, 36 recruiting
- Recruiting
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322
Site Public Contact, 404-778-1868
Kimberly Hoang
- Recruiting
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Site Public Contact, 800-804-9376
Ashley L. Sumrall
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Site Public Contact, 312-695-1301, cancer@northwestern.edu
Karan Dixit
- Recruiting
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Site Public Contact, 773-702-8222, cancerclinicaltrials@bsd.uchicago.edu
Lauren Singer
- Active, not recruiting
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Site Public Contact, 800-293-5066, Jamesline@osumc.edu
Hamid R. Mohtashami
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Active, not recruiting
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
- Recruiting
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Doral
Doral, Florida, 33166
Site Public Contact, kginnity@med.miami.edu
Macarena I. De La Fuente
- Recruiting
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Site Public Contact, 800-826-4673, becomingapatient@coh.org
Stephanie M. Yoon
- Recruiting
University of Kansas Clinical Research Center
Fairway, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
UM Sylvester Comprehensive Cancer Center at Hollywood
Hollywood, Florida, 33021
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Jerica M. Lomax
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
UC San Diego Moores Cancer Center
La Jolla, California, 92093
Site Public Contact, 858-822-5354, cancercto@ucsd.edu
David E. Piccioni
- Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
John L. Villano
- Recruiting
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Brett A. Morris
- Recruiting
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Site Public Contact, 800-622-8922, clinicaltrials@cancer.wisc.edu
Brett A. Morris
- Recruiting
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Site Public Contact, 212-263-4432, cancertrials@nyulangone.org
Marissa Barbaro
- Recruiting
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Site Public Contact, 800-811-8480
Alexander C. Mohler
- Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Nicholas A. Blondin
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Site Public Contact, CancerTrials@nyulangone.org
Marissa Barbaro
- Recruiting
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Site Public Contact, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu
Peter C. Pan
- Recruiting
University of Miami Sylvester Comprehensive Cancer Center at Sole Mia
North Miami, Florida, 33181
Site Public Contact, kginnity@med.miami.edu
Macarena I. De La Fuente
- Recruiting
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Site Public Contact, 405-271-8777, ou-clinical-trials@ouhsc.edu
James D. Battiste
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Jerica M. Lomax
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Megan Mantica
- Recruiting
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324
Site Public Contact, 305-243-2647
Macarena I. De La Fuente
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Timothy J. Harris
- Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Orwa Aboud
- Recruiting
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Site Public Contact, 888-424-2100, cancerinfo@hci.utah.edu
Joe S. Mendez
- Active, not recruiting
Memorial Hospital East
Shiloh, Illinois, 62269
- Active, not recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
- Active, not recruiting
Siteman Cancer Center-South County
St Louis, Missouri, 63129
- Active, not recruiting
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
- Recruiting
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Nicholas A. Blondin
- Suspended
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
- Recruiting
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205
Site Public Contact, 913-588-3671, KUCC_Navigation@kumc.edu
Tolga Tuncer
- Recruiting
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Site Public Contact, 336-713-6771
Roy E. Strowd
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- Conditions
- Astrocytoma, IDH-Mutant, Grade 2, Recurrent Adult Diffuse Hemispheric Glioma, H3 G34-Mutant, Recurrent Adult Diffuse Midline Glioma, H3 K27-Mutant, Recurrent Astrocytoma, IDH-Mutant, Recurrent Astrocytoma, IDH-Mutant, Grade 3, Recurrent Astrocytoma, IDH-Mutant, Grade 4
- Being tested
- Biospecimen Collection, Computed Tomography, Intensity-Modulated Radiation Therapy, Magnetic Resonance Imaging, Triapine
- Medical subject headings
- Astrocytoma, Lymphoma, Follicular, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood and CSF sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
Intensity-Modulated Radiation TherapyRadiation
Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy
Undergo IMRT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
TriapineDrug
Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (IMRT, triapine) | Experimental | 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Drug: Triapine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicity
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.
Measured: Up to 28 days
Secondary outcomes (6)
Response rate
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.
Measured: Up to 5 years
Plasma pharmacokinetic (PK) parameters
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.
Measured: Up to 2 weeks
Progression-free survival
Will be estimated using Kaplan Meier curves.
Measured: From study enrollment to date of either disease progression or death, assessed up to 5 years
Overall survival
Will be estimated using Kaplan Meier curves.
Measured: From study enrollment to date of death, assessed up to 5 years
Proportion of patients who initiated bevacizumab for symptom control
Will be calculated using descriptive statistics.
Measured: Up to 5 years
Tumor tissue biomarkers
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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start30 Jul 2025
- Primary completion30 Jun 2027 (estimated)
- Study completion30 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Astrocytoma, IDH-Mutant, Grade 2Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephanie M Yoon, Principal investigator, City of Hope Comprehensive Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06860594
- Sponsor's protocol ID
- NCI-2025-01531
- Other IDs
- NCI-2025-01531, PHI-151, 10699, 10699, UM1CA186717
- Status last verified
- Jun 2026
- First submitted
- 5 Mar 2025
- Last updated
- 21 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.