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Recurrent Glioblastoma, IDH-WildtypePhase 1NCT06410248

Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma

A Phase 1 study testing Biospecimen Collection, Magnetic Resonance Imaging and Questionnaire Administration in people with Recurrent Glioblastoma, IDH-Wildtype and Recurrent WHO Grade 2 Glioma, run by Northwestern University at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Magnetic Resonance Imaging and Questionnaire Administration
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
23 Jul 2024to 31 Aug 2030
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 confirmed World Health Organization (WHO) grade 2-4 glioma, isocitrate dehydrogenase (IDH) wild type (WT) (by immunohistochemistry [IHC] R132H negative [neg] or sequencing). Astrocytoma with molecular features of glioblastoma (GBM). Confirmed diagnosis via molecular testing
  • Patients must have an established diagnosis of recurrent glioblastoma and:
  • Group 1 and 2: recurrent glioblastoma
  • Group 3: Surgically amenable recurrent glioblastoma
  • Patients must have stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg dexamethasone, for ≥ 7 days prior to registration
  • Patients with 3 or fewer lines of prior therapy
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  • Patients with a life expectancy of at least 3 months
  • Patients with disease that has progressed after a standard or investigational first-line therapy (e.g. radiotherapy [RT], RT plus temozolomide) with or without tumor treating fields therapy (TTFields)
  • Note: Patients who have received fractionated first-line radiation therapy and no prior chemotherapy (e.g. as common practice for MGMT unmethylated tumors), or who have participated in an investigational protocol substituting TMZ for a novel agent are eligible
  • Patients must be able to undergo contrast-enhanced magnetic resonance imaging (MRI)
  • Patients must be age ≥ 18 years
  • Patients must exhibit a Karnofsky performance status ≥ 70
  • Patients must have adequate organ and bone marrow function as defined below: Leukocytes (white blood cells [WBC]) ≥ 3,000/mcL, Absolute neutrophil count (ANC) ≥ 1,500/mcL, Hemoglobin (Hgb) ≥ 8 g/dL (transfusion may be used for eligibility outside of 7 days), Platelets (PLT) ≥ 100,000/mcL (transfusion or growth factor may be used for eligibility outside of 7 days), Total bilirubin ≤ 2 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 institutional ULN, International normalized ratio (INR) ≤ 1.5 x ULN, Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 x ULN
  • 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
  • Patients of child-bearing potential (POCBP) must agree to use two forms of adequate contraception (hormonal or barrier method of birth control, abstinence) from time of informed consent and for the duration of study participation. Patients who can impregnate their partners must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) from time of informed consent and for the duration of study participation
  • Should a patient become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.
  • Note: At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Note: A POCBP is any person with an egg-producing reproductive tract (regardless of gender, sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy
  • Has had menses at any time in the preceding 12 consecutive months (and therefore has not been naturally postmenopausal for > 12 months) (in patients > 45 years of age in the absence of other biological or physiological causes)
  • Potential POCBP who may be menopausal and are < 55 years of age must have a serum follicle-stimulating hormone (FSH) level > 40 mIU/mL to confirm menopause
  • Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff
  • Patient must be willing and able to comply with the protocol for the duration of the study and provide written, signed, and dated informed consent prior to study registration.
  • Patients must have the ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients who have a prior or concurrent malignancy that may interfere with study treatment or safety
  • NOTE: 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, per principal investigator (PI) discretion
  • Patients who are receiving any other investigational agents.
  • Exceptions: COVID-19 vaccine and treatment is allowed, per PI's discretion
  • Patient's interval since last therapy ≥ 1 cycle or ≥ 2 biological half-lives, i.e.
  • ≥ 28 days since start of last cycle of temozolomide (cycle length-28 days)
Show all 27Show fewer
  • ≥ 42 days since start of last cycle of lomustine or other nitrosourea (cycle length-42 days)
  • ≥ 21 days since start of last cycle of a small molecule targeted agent (cycle length-21 days)
  • ≥ 42 days from last bevacizumab infusion (cycle length-42 days)
  • Patients who have a history of allergic reactions attributed to compounds of similar chemical composition to temozolomide or triapine
  • Patients with brainstem, spinal cord and diffuse leptomeningeal dissemination.
  • Patients with gliomatosis or multifocal disease
  • Patients with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD levels prior to registration
  • Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following:
  • Have uncontrolled epilepsy
  • Have an uncontrolled intercurrent illness
  • Are pregnant or nursing
  • Concurrent malignancy (outside of glioblastoma) that requires tumor directed treatment
  • Known concurrent shingles, herpes, cytomegalovirus (CMV) infection
  • Known concurrent opportunistic fungal infection
  • Known immunodeficiency that could lead to opportunistic infections
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
  • Patients who are pregnant or nursing. Pregnant patients are excluded from this study because temozolomide is an alkylating agent with 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 temozolomide, breastfeeding should be discontinued if the mother is treated with temozolomide
  • Patients who are unable to swallow oral medication or have problems/diseases that affect absorption or oral medication
  • Patients with a known history of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). If patient does not have a known history testing will not be conducted
  • Note: Temozolomide is an immunosuppressive agent. Patients with a known history of HIV, HBV, and HCV, and unexplained opportunistic infections are not eligible due to safety reasons

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Study Coordinator contact

3126951301

cancer@northwestern.edu

United States1 site, 1 recruiting

  • Northwestern University

    Chicago, Illinois, 60611

    Karan Dixit, 312-503-1818, karan.dixit@northwetstern.edu

    Karan Dixit

    Recruiting

Other trials in United States

About this study

Official title: A Phase 1 Adaptive Dose Escalation With Dose Expansion Study of Triapine in Combination With Temozolomide (TMZ) for Patients With Recurrent Glioblastoma

This phase I trial tests the safety, side effects, and best dose of triapine in combination with temozolomide in treating patients with glioblastoma that has come back after a period of improvement (recurrent). Triapine inhibits an enzyme responsible for producing molecules required for the production of deoxyribonucleic acid (DNA), which may inhibit tumor cell growth. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill tumor cells and slow down or stop tumor growth. Giving triapine in combination with temozolomide may be safe, tolerable, and/or effective in treating patients with recurrent glioblastoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the recommended phase 2 dose (RP2D) for triapine (3-AP) in combination with temozolomide (TMZ).

SECONDARY OBJECTIVES:

  1. To evaluate the safety profile of triapine in combination with temozolomide (TMZ).

II. To evaluate progression-free survival (PFS). III. To evaluate overall survival (OS). IV. To evaluate the overall response rate (ORR) per RANO 2.0 criteria.

EXPLORATORY OBJECTIVES:

  1. To investigate the distribution of triapine within tumor and peritumoral areas post oral administration and correlation with serum levels.

II. To investigate the potential interaction of drug absorption when administrating oral triapine and temozolomide together by measuring plasma levels triapine and temozolomide post administration.

III. To evaluate oral triapine plasma pharmacokinetics and corresponding methemoglobin level by venous blood gas proportion.

IV. To evaluate the quality of life per Functional Assessment of Cancer Therapy-Brain (FACT-Br) for patients treated with triapine and temozolomide.

  1. To longitudinally track plasma cfDNA fragmentomic patterns to evaluate tumor evolution in patients with recurrent high-grade glioma receiving combination of Triapine and TMZ.

OUTLINE: This is a dose-escalation study of triapine in combination with temozolomide. Patients with recurrent glioblastoma not planning to undergo surgery are assigned to group 1 or group 2. Patients with recurrent glioblastoma planning to undergo surgery are assigned to group 3.

GROUPS 1 AND 2: Patients receive temozolomide orally (PO) once daily (QD) and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) at screening and on study and undergo collection of blood samples on study.

GROUP 3: Patients receive triapine PO QD for 5 days prior to surgical resection. After surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 24 months.

Being tested
Biospecimen Collection, Magnetic Resonance Imaging, Questionnaire Administration, Resection, Temozolomide
Medical subject headings
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, Specimen Collection

    Undergo collection of blood samples

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Questionnaire AdministrationOther

    Ancillary studies

  • ResectionProcedure or surgery

    Also called Surgical Resection

    Undergo surgical resection

  • TemozolomideDrug

    Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831

    Given PO

  • TriapineDrug

    Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191

    Given PO

Study groups in NCT06410248
Study groupRoleWhat they receive
Group 3 (triapine, surgical resection, temozolomide)ExperimentalPatients receive triapine PO QD for 5 days prior to surgical resection. After surgical resection, patients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.
Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Procedure: Resection; Drug: Temozolomide; Drug: Triapine
Groups 1 and 2 (temozolomide, triapine)ExperimentalPatients receive temozolomide PO QD and triapine PO QD on days 1-5 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI at screening and on study and undergo collection of blood samples on study.
Receives: Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Temozolomide; Drug: Triapine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase 2 dose for triapine in combination with temozolomide

    The recommended phase 2 dose will be based on treatment-emergent and drug-related toxicity. Dose limiting toxicities and adverse events (AEs) will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0.

    Measured: At the end of Cycle 1 (each cycle is 28 days) + 7 days (up to cycle 2 day 7)

Secondary outcomes (4)

  1. Incidence of AEs and serious AEs

    Will evaluate the occurrence of toxicity (AEs and serious AEs) and the number of patients who discontinue treatment due to toxicity. Toxicity will be assessed by CTCAE v. 5.0. Adverse events will be sorted (by type, severity [grade], timing, and attribution to triapine), collected, and reported according to CTCAE v5.0.

    Measured: Up to 30 days after last administration of study drug

  2. Progression free survival (PFS)

    Progression will be determined by clinical progression or by radiographic imaging as assessed by Response Assessment in Neuro-Oncology (RANO) criteria. The median and corresponding 95% confidence interval will also be estimated.

    Measured: From baseline until the patient experiences disease progression, initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause, assessed at 6, 12, and 24 months

  3. Overall survival

    Will be described by Kaplan-Meier curve. The median and corresponding 95% confidence interval will also be estimated.

    Measured: From time of diagnosis until the patient initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause, assessed at 6, 12, and 24 months

  4. Overall response rate (ORR)

    ORR will be assessed by RANO criteria. To determine the ORR, this endpoint will calculate the proportion of treated patients who experience an overall response (complete response [CR] or partial response [PR] per RANO criteria). The date of first response for either CR or PR will be used for the calculation of ORR. Will be estimated using the expansion cohort, along with its 95% confidence interval.

    Measured: From baseline until the response has been confirmed, the patient experiences disease progression, the patient initiates, subsequent anti-cancer therapy, or the patient completes study participation, assessed up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2024
  2. Study start23 Jul 2024
  3. Primary completion22 Jul 2026
  4. Study completion31 Aug 2030 (estimated)

Resources

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
22 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06410248
Sponsor's protocol ID
NU 23C05
Other IDs
NCI-2024-02351, STU00220426, NU 23C05, P30CA060553
Status last verified
Sep 2026
First submitted
6 May 2024
Last updated
9 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biospecimen Collection, Magnetic Resonance Imaging and Questionnaire Administration in people with Recurrent Glioblastoma, IDH-Wildtype and Recurrent WHO Grade 2 Glioma, run by Northwestern University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Study Coordinator (3126951301, cancer@northwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase 2 dose for triapine in combination with temozolomide (time frame: At the end of Cycle 1 (each cycle is 28 days) + 7 days (up to cycle 2 day 7)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06410248.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2026.

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