Infigratinib in Recurrent High-Grade Glioma Patients

Stopped early · Early Phase 1

Conditions studied: Glioma, Glioblastoma, GBM

In brief

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.

Key facts

Study ID

NCT04424966

Run by

Nader Sanai

People needed

7

Starts

2020-07-21

Expected to finish

2024-02-19

Last updated by the study team

2025-10-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• hemoglobin ≥8.0 g/dL Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator.
• Adequate hepatic and renal function:
• total bilirubin ≤1.5 X ULN Participants with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• AST(SGOT) ≤3 X institutional ULN
• ALT(SGPT) ≤3 X institutional ULN
• Calculated or measured creatinine clearance ≥45 mL/min
• Other Lab Values:
• Amylase or lipase ≤2 X institutional ULN
• calcium or phosphorus, or calcium-phosphorus product <55 mg2/dL2
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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.
• Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• Prior therapy with any mitogen-activated protein kinase (MEK) or FGFR inhibitor. Prior therapy is defined as a therapeutic dosing, as determined by the Investigator.
• Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Participants are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone.
• Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.
• Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents, infigratinib, or their excipients.
• Treatment with another investigational drug or other intervention within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer.
• Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug.
• Have used medications known to prolong the QT interval and/or are associated with a risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.
• Have used amiodarone within 90 days prior to first dose of study drug.

Where it is running

• Chandler Regional Medical Center — Chandler, Arizona, United States
• St. Joseph's Hospital and Medical Center — Phoenix, Arizona, United States
• HonorHealth Scottsdale Osborn Medical Center — Scottsdale, Arizona, United States

Full record on ClinicalTrials.gov

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