RECRUITING

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

Conditions

Recurrent Glioma Recurrent WHO Grade 2 Glioma Recurrent WHO Grade 3 Glioma Recurrent WHO Grade 4 Glioma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2024-01-04

Study Completion:2026-10-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05859334

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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 * Patient understands the procedures and investigational nature of the study drug and agrees to comply with study requirements by providing written informed consent * Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%) * Absolute neutrophil count \>= 1000/uL * Hemoglobin \> 8 g/dL (Patients are allowed to be transfused to this level) * Platelets \>= 100 x 10\^9/L * Serum total bilirubin =\< 1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement following approval by the medical monitor * Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN * Creatinine clearance \> 30 mL/min (patients with mild or moderate renal impairment) based on the Cockroft-Gault glomerular filtration rate (GFR) estimation * Patient must have normal serum phosphate level as per local laboratory parameters. (Medical management allowed) * Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or chemotherapy treatment with temozolomide * 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 should be New York Heart Association Functional Classification class 2B or better * The effects of erdafitinib on the developing human fetus are unknown. For this reason and because FGFR inhibitors 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 one month after completion of erdafitinib administration. 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 one month after completion of erdafitinib 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	* 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

Inclusion Criteria

Exclusion Criteria

* 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
* Patient understands the procedures and investigational nature of the study drug and agrees to comply with study requirements by providing written informed consent
* Patient must have Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
* Absolute neutrophil count \>= 1000/uL
* Hemoglobin \> 8 g/dL (Patients are allowed to be transfused to this level)
* Platelets \>= 100 x 10\^9/L
* Serum total bilirubin =\< 1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease or disease involvement following approval by the medical monitor
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN
* Creatinine clearance \> 30 mL/min (patients with mild or moderate renal impairment) based on the Cockroft-Gault glomerular filtration rate (GFR) estimation
* Patient must have normal serum phosphate level as per local laboratory parameters. (Medical management allowed)
* Patient must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or chemotherapy treatment with temozolomide
* 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 should be New York Heart Association Functional Classification class 2B or better
* The effects of erdafitinib on the developing human fetus are unknown. For this reason and because FGFR inhibitors 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 one month after completion of erdafitinib administration. 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 one month after completion of erdafitinib 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

* 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

Contacts and Locations

Principal Investigator

Macarena I De La Fuente

PRINCIPAL_INVESTIGATOR

University Health Network Princess Margaret Cancer Center LAO

Study Locations (Sites)

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

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

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Macarena I De La Fuente, PRINCIPAL_INVESTIGATOR, University Health Network Princess Margaret Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-04

Study Completion Date2026-10-23

Study Record Updates

Study Start Date2024-01-04

Study Completion Date2026-10-23

Terms related to this study

Additional Relevant MeSH Terms

Recurrent Glioma
Recurrent WHO Grade 2 Glioma
Recurrent WHO Grade 3 Glioma
Recurrent WHO Grade 4 Glioma