Trial Title:
Testing the Anti-cancer Drug Erdafitinib for Brain Cancers That Have Returned or Progressed Following Treatment
NCT ID:
NCT05859334
Condition:
Recurrent Glioblastoma, IDH-Wildtype
Recurrent WHO Grade 2 Glioma
Recurrent WHO Grade 3 Glioma
Conditions: Official terms:
Glioblastoma
Glioma
Recurrence
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Treatment (erdafitinib)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Erdafitinib
Description:
Given PO
Arm group label:
Treatment (erdafitinib)
Other name:
Balversa
Other name:
JNJ 42756493
Other name:
JNJ-42756493
Other name:
JNJ42756493
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (erdafitinib)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Procedure
Intervention name:
Optical Coherence Tomography
Description:
Undergo OCT
Arm group label:
Treatment (erdafitinib)
Other name:
OCT
Other name:
Optical Coherence Tomography (OCT)
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion 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/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
Exclusion Criteria:
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCHealth University of Colorado Hospital
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
720-848-0650
Investigator:
Last name:
Douglas E. Ney
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Coral Gables
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Macarena I. De La Fuente
Email:
Principal Investigator
Facility:
Name:
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Macarena I. De La Fuente
Email:
Principal Investigator
Facility:
Name:
University of Miami Miller School of Medicine-Sylvester Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
305-243-2647
Investigator:
Last name:
Macarena I. De La Fuente
Email:
Principal Investigator
Facility:
Name:
Memorial Hospital East
Address:
City:
Shiloh
Zip:
62269
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
314-747-9912
Email:
dschwab@wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at West County Hospital
Address:
City:
Creve Coeur
Zip:
63141
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Christian Hospital
Address:
City:
Saint Louis
Zip:
63136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Siteman Cancer Center at Saint Peters Hospital
Address:
City:
Saint Peters
Zip:
63376
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-600-3606
Email:
info@siteman.wustl.edu
Investigator:
Last name:
Omar H. Butt
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Basking Ridge
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
551-996-2897
Investigator:
Last name:
Deric M. Park
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Monmouth
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Bergen
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Commack
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Westchester
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Email:
CancerTrials@nyulangone.org
Investigator:
Last name:
Maria del Pilar Guillermo Prieto Eibl
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Nassau
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
212-639-7592
Investigator:
Last name:
Thomas J. Kaley
Email:
Principal Investigator
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
405-271-8777
Email:
ou-clinical-trials@ouhsc.edu
Investigator:
Last name:
James D. Battiste
Email:
Principal Investigator
Facility:
Name:
Huntsman Cancer Institute/University of Utah
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
888-424-2100
Email:
cancerinfo@hci.utah.edu
Investigator:
Last name:
Howard Colman
Email:
Principal Investigator
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Contact:
Last name:
Site Public Contact
Phone:
800-622-8922
Email:
clinicaltrials@cancer.wisc.edu
Investigator:
Last name:
Ankush Bhatia
Email:
Principal Investigator
Facility:
Name:
University Health Network Princess Margaret Cancer Center LAO
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Contact:
Last name:
Macarena I. De La Fuente
Phone:
305-243-4951
Email:
mdelafuente@med.miami.edu
Investigator:
Last name:
Macarena I. De La Fuente
Email:
Principal Investigator
Start date:
January 4, 2024
Completion date:
October 23, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05859334
