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

Status: Recruiting
Location: See all (27) locations...
Intervention Type: Procedure, Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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

Locations
United States
Colorado
UCHealth University of Colorado Hospital
RECRUITING
Aurora
Florida
UM Sylvester Comprehensive Cancer Center at Coral Gables
RECRUITING
Coral Gables
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
RECRUITING
Deerfield Beach
University of Miami Miller School of Medicine-Sylvester Cancer Center
RECRUITING
Miami
Illinois
Memorial Hospital East
RECRUITING
Shiloh
Missouri
Siteman Cancer Center at Saint Peters Hospital
RECRUITING
City Of Saint Peters
Siteman Cancer Center at West County Hospital
RECRUITING
Creve Coeur
Siteman Cancer Center at Christian Hospital
RECRUITING
St Louis
Siteman Cancer Center-South County
RECRUITING
St Louis
Washington University School of Medicine
RECRUITING
St Louis
North Carolina
Wake Forest University Health Sciences
RECRUITING
Winston-salem
New Jersey
Memorial Sloan Kettering Basking Ridge
RECRUITING
Basking Ridge
Hackensack University Medical Center
RECRUITING
Hackensack
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
Laura and Isaac Perlmutter Cancer Center at NYU Langone
RECRUITING
New York
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
RECRUITING
New York
Memorial Sloan Kettering Nassau
RECRUITING
Uniondale
Oklahoma
University of Oklahoma Health Sciences Center
RECRUITING
Oklahoma City
Texas
UT Southwestern/Simmons Cancer Center-Dallas
RECRUITING
Dallas
M D Anderson Cancer Center
RECRUITING
Houston
Utah
Huntsman Cancer Institute/University of Utah
RECRUITING
Salt Lake City
Wisconsin
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
RECRUITING
Madison
University of Wisconsin Carbone Cancer Center - University Hospital
RECRUITING
Madison
Time Frame
Start Date: 2024-01-04
Estimated Completion Date: 2026-10-23
Participants
Target number of participants: 35
Treatments
Experimental: Treatment (erdafitinib)
Patients 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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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