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

NCT06410248 | Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: NU 23C05NCI-2024-02351STU00220426P30CA060553
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Recurrent Glioblastoma, IDH-Wildtype; Recurrent WHO Grade 2 Glioma; Recurrent WHO Grade 3 Glioma; Recurrent WHO Grade 4 Glioma

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Incidence of AEs and serious AEs

  Up to 30 days after last administration of study drug

• Progression free survival (PFS)

  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

• Overall survival

  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

• Overall response rate (ORR)

  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

Study Arms (2)

Group 3 (triapine, surgical resection, temozolomide)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Procedure: Resection; Drug: Temozolomide; Drug: Triapine

Groups 1 and 2 (temozolomide, triapine)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Other: Questionnaire Administration; Drug: Temozolomide; Drug: Triapine

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

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

Group 3 (triapine, surgical resection, temozolomide); Groups 1 and 2 (temozolomide, 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

Group 3 (triapine, surgical resection, temozolomide); Groups 1 and 2 (temozolomide, triapine)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Group 3 (triapine, surgical resection, temozolomide)

Triapine DRUG

Given PO

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

Group 3 (triapine, surgical resection, temozolomide); Groups 1 and 2 (temozolomide, triapine)

Questionnaire Administration OTHER

Ancillary studies

Group 3 (triapine, surgical resection, temozolomide); Groups 1 and 2 (temozolomide, triapine)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temizole, Temodal, Temodar, Temomedac, TMZ

Group 3 (triapine, surgical resection, temozolomide); Groups 1 and 2 (temozolomide, triapine)

Eligibility Criteria

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

You may qualify if:

• 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 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
• 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)

You may not qualify if:

• 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 cytotoxic therapy ≥ 1 cycle or ≥ 2 biological half-lives, i.e.
• ≥ 28 days since start of last cycle of temozolomide (cycle length-28 days)
• ≥ 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 spinal cord and diffuse leptomeningeal dissemination
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• Northwestern University: lead
• BrainUp Inc: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

MeSH Terms

Conditions

Glioblastoma

Interventions

Specimen Handling; Magnetic Resonance Spectroscopy; Temozolomide; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Karan Dixit, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Coordinator

CONTACT

3126951301; cancer@northwestern.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2024
• First Posted: May 13, 2024
• Study Start: July 23, 2024
• Primary Completion (Estimated): May 12, 2029
• Study Completion (Estimated): May 12, 2030
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

US (1)