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
3 other identifiers
interventional
30
1 country
27
Brief Summary
This phase II trial tests how well erdafitinib works in controlling IDH-wild type (WT), FGFR-TACC gene fusion positive gliomas that have come back after a period of improvement (recurrent) or that are growing, spreading, or getting worse (progressive). 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2024
Typical duration for phase_2
27 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 13, 2023
CompletedFirst Posted
Study publicly available on registry
May 16, 2023
CompletedStudy Start
First participant enrolled
January 4, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 23, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 23, 2026
April 23, 2026
March 1, 2026
2.8 years
May 13, 2023
April 22, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Objective response rate
Defined as the proportion of patients with either complete response or partial response as per Response Assessment in Neuro-Oncology (RANO) or RANO-low-grade glioma 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 and corresponding 95% confidence intervals and p-values will be reported.
Up to 2 years
Secondary Outcomes (4)
Incidence of dose-limiting toxicities
Up to 28 days
Incidence of adverse events (AEs) and serious AEs
Up to 2 years
Progression-free survival
Time between date of enrollment and date of progression or date of death from any cause, assessed at 6 months
Overall survival
Time between the date of enrollment and date of death from any cause, censored at the last date of follow-up, assessed up to 2 years
Study Arms (1)
Treatment (erdafitinib)
EXPERIMENTALPatients receive erdafitinib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI, OCT, and collection of blood samples throughout the trial. Additionally, patients may optionally undergo collection of tissue samples on study.
Interventions
Given PO
Undergo MRI
Undergo OCT
Undergo collection of blood and/or tissue samples
Eligibility Criteria
You may qualify if:
- Patient must be \>= 18 years of age
- Patient must have histologically confirmed IDH-WT gliomas (grade 2-4) as per World Health Organization (WHO) 2016 or 2021 classification
- Tumor tissue should be positive for FGFR-TACC gene fusion as per any local next generation sequencing (NGS) (Clinical Laboratory Improvement Act \[CLIA\]-approved) assay described in background section
- The disease should be recurrent or progressive glioma after initial anti-tumor treatment with at least 1 line of treatment including surgical resection, radiation therapy and/or chemotherapy
- For patients with WHO grade 3 or 4 glioma and progressive disease \< 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
- New enhancement outside of the radiation field (beyond the high-dose region or 80% isodose line)
- If there is unequivocal evidence of viable tumor on histopathologic sampling (e.g., solid tumor areas. i.e., \> 70% tumor cell nuclei in areas), high or progressive increase in Ki-67 proliferation index compared with prior biopsy, or evidence for histologic progression or increased anaplasia in tumor)
- For patients with WHO grade 3 or 4 glioma and progressive disease \>= 12 weeks after completion of chemoradiotherapy, progression can be defined by the following set of criteria:
- New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids
- Increase by \>= 25% in the sum of the products of perpendicular diameters between the first post-radiotherapy scan, or a subsequent scan with smaller tumor size, and the scan at 12 weeks or later on stable or increasing doses of corticosteroids
- For patients receiving antiangiogenic therapy, significant increase in T2/fluid attenuated inversion recovery (FLAIR) non-enhancing lesion may also be considered progressive disease. The increased T2/FLAIR must have occurred with the patient on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy and not be a result of comorbid events (e.g., effects of radiation therapy, demyelination, ischemic injury, infection, seizures, postoperative changes, or other treatment effects)
- For patients with WHO grade 2 glioma progression is defined by any one of the following:
- Development of new lesions or increase of enhancement (radiological evidence of malignant transformation)
- A 25% increase of the T2 or FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after initiation of therapy, not attributable to radiation effect or to comorbid events
- There must be measurable disease (enhancing or non-enhancing as per Response Assessment in Neuro-Oncology \[RANO\] or RANO-low-grade glioma \[LGG\] criteria), as evaluated on pre-treatment MRI
- +16 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to erdafitinib
- Patients requiring any medications or substances that are moderate CYP2C9 inducers and strong CYP3A4 inducers are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with uncontrolled intercurrent illness
- Pregnant women are excluded from this study because erdafitinib is an FGFR 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 erdafitinib, breastfeeding should be discontinued if the mother is treated with erdafitinib
- Current central serous retinopathy (CSR) or retinal pigment epithelial detachment of any grade
- Corrected QT interval (QTc) prolongation as confirmed by electrocardiography (ECG) at screening (Fridericia; QTc \> 480 milliseconds)
- Patients who have previously received FGFR inhibitors
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (27)
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Macarena I De La Fuente
University Health Network Princess Margaret Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 13, 2023
First Posted
May 16, 2023
Study Start
January 4, 2024
Primary Completion (Estimated)
October 23, 2026
Study Completion (Estimated)
October 23, 2026
Last Updated
April 23, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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.