Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Glioma

Disease Attributes

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

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.

Biospecimen Collection

Magnetic Resonance Imaging

Questionnaire Administration

Resection

Triapine

Study Coordinator

Karan Dixit

Karan Dixit, MD

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.

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. 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 Response Assessment in Neuro-Oncology (RANO) criteria.

EXPLORATORY OBJECTIVES:

I. 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.

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.

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

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

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.

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.

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.

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

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.

National Cancer Institute (NCI)

BrainUp Inc

Northwestern University

Nervous System Diseases

Brain Neoplasms

Patients receive erdafitinib PO QD in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI, OCT, and collection of blood samples throughout the trial.

Erdafitinib

Optical Coherence Tomography

Site Public Contact

Douglas E. Ney

Macarena I. De La Fuente

Omar H. Butt

Thomas J. Kaley

Deric M. Park

James D. Battiste

Howard Colman

Ankush Bhatia

Macarena I De La Fuente

This phase II trial tests how well erdafitinib works in controlling IDH-wild type (WT) gliomas with FGFR-TACC gene fusion that have returned or that have grown, spread, or gotten worse (progressed). Erdafitinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal FGFR protein that signals tumor cells to multiply. This may help keep tumor cells from growing and may kill them. Giving erdafitinib may help to slow the growth of or to shrink tumor cells in patients with recurrent or progressive IDH-wild type gliomas with FGFR-TACC gene fusion.

PRIMARY OBJECTIVE:

I. To assess the preliminary anti-tumor activity of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion as measured by the best response at any time during treatment in terms of objective response rate (ORR).

SECONDARY OBJECTIVES:

I. To determine the safety and tolerability of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion.

II. To assess the overall survival (OS) of erdafitinib in patients with recurrent or progressive IDH-WT glioma with FGFR-TACC gene fusion.

III. To assess the progression free survival (PFS) at 6 months of patient with IDH-WT glioma with FGFR-TACC gene fusion treated with erdafitinib.

OUTLINE: This is a dose-escalation study of erdafitinib followed by a dose-expansion study.

Patients receive erdafitinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI), optical coherence tomography (OCT), and collection of blood samples throughout the trial.

After study completion, patients are followed up every 3 months for 2 years.

Testing the Anti-cancer Drug Erdafitinib for Brain Cancers That Have Returned or Progressed Following Treatment

A Phase 2 Study of Erdafitinib in Patients With Recurrent or Progressive IDH-Wild Type Glioma With an FGFR-TACC Gene Fusion

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.

Defined as the proportion of patients with either complete response or partial response as per Response Assessment in Neuro-Oncology (RANO) criteria. The response rate will be estimated along with the corresponding 95% confidence interval using the binomial exact method. Univariable and multivariable logistic regression models will be used to estimate the associations between study covariates and response status. Odds ratios (ORs) and corresponding 95% confidence intervals and p-values will be reported.

Analyzed based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

PFS is defined as the elapsed time between the date of enrollment and the date of progression or date of death from any cause. Alive patients without progression will be censored at the last date of follow-up. Kaplan-Meier method will be used to estimate survival rates for pre-specified time points along with 95% confidence intervals. Hazard ratios (HRs) will be estimated using Cox proportional hazards regression model to examine the associations of study covariates with time-to-event outcomes along with corresponding 95% confidence intervals and p-values if these are estimable.

Kaplan-Meier method will be used to estimate survival rates for pre-specified time points along with 95% confidence intervals. Hazard ratios (HRs) will be estimated using Cox proportional hazards regression model to examine the associations of study covariates with time-to-event outcomes along with corresponding 95% confidence intervals and p-values if these are estimable.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Triapine in Combination With Temozolomide for the Treatment of Patients With Recurrent Glioblastoma	NCT06410248	Recurrent Gliob... Recurrent WHO G... Recurrent WHO G... Recurrent WHO G...	Biospecimen Col... Magnetic Resona... Questionnaire A... Resection Temozolomide Triapine	18 Years -	Northwestern University
Testing the Anti-cancer Drug Erdafitinib for Brain Cancers That Have Returned or Progressed Following Treatment	NCT05859334	Recurrent Gliob... Recurrent WHO G... Recurrent WHO G...	Biospecimen Col... Erdafitinib Magnetic Resona... Optical Coheren...	18 Years -	National Cancer Institute (NCI)

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