Infigratinib in Recurrent High-Grade Glioma Patients

NCT04424966 | Terminated Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2020-0820-500-092-34-38
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

This trial is an open-label, multicenter, Phase 0 trial that will enroll up to 20 participants with recurrent high-grade glioma with FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3 translocation which are scheduled for resection. In the lead-in cohort, a total of 20 participants will be enrolled into the proposed phase 0 clinical trial. Participants will be administered infigratinib prior to surgical resection of their tumor.

Conditions

Glioma; Glioblastoma; GBM

Outcome Measures

Primary Outcomes (7)

• Total Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue

  Phase 0: Total infigratinib concentration in Gd enhancing and Gd non-enhancing tumor tissue collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• Unbound Concentration of Infigratinib in Enhancing and Non-Enhancing Tumor Tissue

  Phase 0: Unbound infigratinib concentration in Gd enhancing and Gd non-enhancing tumor tissue collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• Total Concentration of Infigratinib in Plasma

  Phase 0: Total infigratinib concentration in blood plasma collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• Unbound Concentration of Infigratinib in Plasma

  Phase 0: Unbound infigratinib concentration in blood plasma collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• Total Concentration of Infigratinib in Cerebrospinal Fluid (CSF)

  Phase 0: Total infigratinib concentration in cerebrospinal fluid (CSF) collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• Unbound Concentration of Infigratinib in Cerebrospinal Fluid (CSF)

  Phase 0: Unbound infigratinib concentration in cerebrospinal fluid (CSF) collected intraoperatively, approximately 8 hours after study drug administration, will be determined by a validated liquid chromatography-mass spectrometry (LC-MS) method.

  Intraoperative

• 6-month Progression-Free Survival (PFS6) in Expansion Phase Participants

  Proportion of participants who remain alive without disease progression at 6 months

  From the date of Phase 0 surgery until the first documentation of disease progression or death due to any cause, assessed up to 6 months

Secondary Outcomes (6)

• Mean % Change of pERK+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

  Baseline, Intraoperatively

• Mean % Change of MIB-1+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

  Baseline, Intraoperatively

• Mean % Change of ClCas3+ Cells in Resected Post-Treatment Recurrent HGG Tissue vs Baseline Tissue

  Baseline, Intraoperatively

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Assessed by CTCAE v5.0

  From date of first dose until 7 days after last dose, assessed over 2 years 6 months

• Number of Participants With Treatment-Related Adverse Events (TRAEs) Assessed by CTCAE v5.0

  From date of first dose until 7 days after last dose, assessed over 2 years 6 months

Other Outcomes (9)

• Total Infigratinib Peak Plasma Concentration (Cmax)

  Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose

• Unbound Infigratinib Peak Plasma Concentration (Cmax)

  Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose

• Total Infigratinib Time to Peak Plasma Concentration (Tmax)

  Day of surgery at pre-dose and 0.5, 1, 2, 4, 6, 8, and 24 hours post-dose

Study Arms (1)

Arm 1

EXPERIMENTAL

Phase 0: 125 mg of infigratinib administered orally for 7 days prior to surgical resection. Expansion Cohort: 125 mg of infigratinib administered orally for 21 days of a 28-day treatment cycles.

Drug: Infigratinib

Interventions

Infigratinib DRUG

The Phase 0 study will include treatment of recurrent high-grade glioma participants with 125 mg of infigratinib 7 days prior to surgical resection. Participants with tumors demonstrating PK-response will continue treatment with the same dose continuously for 21 days in 28-day cycles after surgery.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as participants who have progressed on or following standard (Stupp regimen) therapy, which included maximal surgical resection, temozolomide, and fractionated radiotherapy.
• Recurrence must be confirmed by diagnostic biopsy with local pathology review or contrast-enhanced MRI.
• Have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.
• Sufficient archival tissue available to confirm eligibility.
• Archival tissue must demonstrate: FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3 translocation from NGS sequencing or IHC and RT-PCR.
• Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).
• Has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.
• Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.
• Age ≥18 at time of consent
• Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982)
• Ability to swallow oral medications.
• Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):
• Adequate bone marrow function:
• absolute neutrophil count ≥1,000/mcL
• Platelets (at time of surgery) ≥100,000/mcL

You may not qualify if:

• Have a history of liver transplant.
• Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
• Known active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system, and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification.
• Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study.
• Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc.
• Have had a recent (≤3 months prior to first dose of study drug) transient ischemic attack or stroke.
• CTCAE (v5.0) Grade ≥2 hearing loss.
• CTCAE (v5.0) Grade ≥2 neuropathy.
• Have clinically significant cardiac disease including any of the following:
• Known congestive heart failure requiring treatment (New York Heart Association Grade ≥2), LVEF \<50% or local lower limit of normal as determined by MUGA scan or echocardiogram (ECHO), or uncontrolled hypertension (refer to the European Society of Cardiology and European Society of Hypertension guidelines \[Williams et al 2018\]).
• Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade ≥2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality.
• Unstable angina pectoris or acute myocardial infarction ≤3 months prior to first dose of study drug.
• QTcF \>470 msec (males and females). Note: If the QTcF is \>470 msec in the first ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is ≤470 msec, the participant meets eligibility in this regard.
• Known history of congenital long QT syndrome.

Sponsors & Collaborators

• Nader Sanai: lead
• Ivy Brain Tumor Center: collaborator
• Barrow Neurological Institute: collaborator
• QED Therapeutics, a BridgeBio company: collaborator

Study Sites (3)

Chandler Regional Medical Center

Chandler, Arizona, 85224, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

HonorHealth Scottsdale Osborn Medical Center

Scottsdale, Arizona, 85251, United States

Location

Related Links

• Ivy Brain Tumor Center Website

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Results Point of Contact

• Title: Dr. Nader Sanai
• Organization: Ivy Brain Tumor Center

research@ivybraintumorcenter.org

602-406-8605

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Ivy Brain Tumor Center

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 11, 2020
• Study Start: July 21, 2020
• Primary Completion: January 31, 2023
• Study Completion: February 19, 2024
• Last Updated: October 24, 2025
• Results First Posted: October 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)