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b'Prior resection of histologically diagnosed high-grade gliomas (III and IV) defined as' |
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b'participants who have progressed on or following standard (Stupp regimen) therapy,' |
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b'which included maximal surgical resection, temozolomide, and fractionated' |
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b'radiotherapy.' |
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b'Recurrence must be confirmed by diagnostic biopsy with local pathology review or' |
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b'contrast-enhanced MRI.' |
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b'Have measurable disease preoperatively, defined as at least 1 contrast-enhancing' |
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b'lesion, with 2 perpendicular measurements of at least 1 cm, as per RANO criteria.' |
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b'Sufficient archival tissue available to confirm eligibility.' |
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b'Archival tissue must demonstrate: FGFR1 K656E or FGFR3 K650E mutation or FGFR3-TACC3' |
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b'translocation from NGS sequencing or IHC and RT-PCR.' |
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b'Ability to understand and the willingness to sign a written informed consent document' |
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b'(personally or by the legally authorized representative, if applicable).' |
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b'Has voluntarily agreed to participate by giving written informed consent (personally' |
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b'or via legally authorized representative(s), and assent if applicable). Written' |
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b'informed consent for the protocol must be obtained prior to any screening procedures.' |
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b'If consent cannot be expressed in writing, it must be formally documented and' |
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b'witnessed, ideally via an independent trusted witness.' |
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b'Willingness and ability to comply with scheduled visits, treatment plans, laboratory' |
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b'tests and other procedures.' |
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b'Age \\u226518 at time of consent' |
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b'Have a performance status (PS) of \\u22642 on the Eastern Cooperative Oncology (Group (ECOG)' |
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b'cale (Oken et al. 1982)' |
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b'Ability to swallow oral medications.' |
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b'Has adequate bone marrow and organ function as defined by the following laboratory' |
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b'values (as assessed by the local laboratory for eligibility):' |
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b'Adequate bone marrow function:' |
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b'absolute neutrophil count \\u22651,000/mcL' |
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b'Platelets (at time of surgery) \\u2265100,000/mcL' |
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b'hemoglobin \\u22658.0 g/dL Participants may receive erythrocyte transfusions to' |
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b'achieve this hemoglobin level at the discretion of the investigator.' |
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b'Adequate hepatic and renal function:' |
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b"total bilirubin \\u22641.5 X ULN Participants with Gilbert's syndrome with a total" |
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b'bilirubin \\u22642.0 times ULN and direct bilirubin within normal limits are' |
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b'permitted.' |
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b'AST(SGOT) \\u22643 X institutional ULN' |
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b'ALT(SGPT) \\u22643 X institutional ULN' |
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b'Calculated or measured creatinine clearance \\u226545 mL/min' |
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b'Other Lab Values:' |
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b'Amylase or lipase \\u22642 X institutional ULN' |
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b'calcium or phosphorus, or calcium-phosphorus product <55 mg2/dL2' |
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b'Inorganic phosphorus within normal limits' |
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b'Total corrected serum calcium within normal limits' |
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b'Confirmed negative serum pregnancy test (\\u03b2-hCG) before starting study treatment or' |
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b'participant has had a hysterectomy.' |
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b'For females of reproductive potential: use of highly effective contraception for at' |
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b'least 1 month prior to screening and agreement to use such a method during study' |
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b'participation and for an additional 3 months after the end of treatment' |
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b'administration.' |
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b'For males of reproductive potential: use of condoms or other methods to ensure' |
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b'effective contraception with partner and for an additional 1 month after the end of' |
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b'treatment administration. A condom is required to be used also by vasectomized men as' |
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b'well as during intercourse with a male partner to prevent delivery of the drug via' |
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b'eminal fluid.' |
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b'Agreement to adhere to Lifestyle Considerations throughout study duration.' |
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b'Participants who received chemotherapy must have recovered (Common Terminology' |
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b'Criteria for Adverse Events [CTCAE] Grade \\u22641) from the acute effects of chemotherapy' |
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b'except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A' |
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b'washout period of at least 21 days is required between last chemotherapy dose and Day' |
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b'1 (provided the patient did not receive radiotherapy).' |
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b'Participants who received radiotherapy must have completed and fully recovered from' |
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b'the acute effects of radiotherapy. A washout period of at least 14 days is required' |
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b'between end of radiotherapy and Day 1.' |
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b'Have a history of liver transplant.'
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b'Have impairment of gastrointestinal (GI) function or GI disease that may significantly'
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b'alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled'
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b'nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).'
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b'Known active systemic bacterial infection (requiring intravenous [IV] antibiotics at'
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b'time of initiating study treatment), fungal infection, or detectable viral infection'
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b'(such as known human immunodeficiency virus positivity or with known active hepatitis'
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b'B or C [for example, hepatitis B surface antigen positive]. Screening is not required'
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b'for enrollment.'
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b'Have a history and/or current evidence of extensive tissue calcification including,'
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b'but not limited to, the soft tissue, kidneys, intestine, myocardium, vascular system,'
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b'and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal'
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b'calcifications, and asymptomatic coronary calcification.'
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b'Have current evidence of corneal or retinal disorder/keratopathy including, but not'
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b'limited to, bullous/band keratopathy, inflammation or ulceration, keratoconjunctivitis'
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b'confirmed by ophthalmic examination. Subjects with asymptomatic ophthalmic conditions'
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b'assessed by the investigator to pose minimal risk for study participation may be'
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b'enrolled in the study.'
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b'Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g.,'
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b'parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis'
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b'etc.'
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b'Have had a recent (\\u22643 months prior to first dose of study drug) transient ischemic'
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b'attack or stroke.'
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b'CTCAE (v5.0) Grade \\u22652 hearing loss.'
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b'CTCAE (v5.0) Grade \\u22652 neuropathy.'
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b'Have clinically significant cardiac disease including any of the following:'
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b'Known congestive heart failure requiring treatment (New York Heart Association'
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b'Grade \\u22652), LVEF <50% or local lower limit of normal as determined by MUGA scan or'
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b'echocardiogram (ECHO), or uncontrolled hypertension (refer to the European'
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b'Society of Cardiology and European Society of Hypertension guidelines [Williams'
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b'et al 2018]).'
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b'Presence of Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade \\u22652'
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b'ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction'
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b'abnormality.'
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b'Unstable angina pectoris or acute myocardial infarction \\u22643 months prior to first'
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b'dose of study drug.'
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b'QTcF >470 msec (males and females). Note: If the QTcF is >470 msec in the first'
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b'ECG, a total of 3 ECGs separated by at least 5 minutes should be performed. If'
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b'the average of these 3 consecutive results for QTcF is \\u2264470 msec, the participant'
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b'meets eligibility in this regard.'
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b'Known history of congenital long QT syndrome.'
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b'Has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment'
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b'of the investigator, would preclude participation in this study (for example,'
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b'interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe'
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b'renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major'
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b"urgical resection involving the stomach or small bowel, or preexisting Crohn's"
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b'disease or ulcerative colitis or a preexisting chronic condition resulting in baseline'
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b'Grade 2 or higher diarrhea).'
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b'Prior therapy with any mitogen-activated protein kinase (MEK) or FGFR inhibitor. Prior'
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b'therapy is defined as a therapeutic dosing, as determined by the Investigator.'
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b'Are currently receiving or are planning to receive during participation in this study,'
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b'treatment with agents that are known strong inducers or inhibitors of CYP3A4 and'
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b'medications which increase serum phosphorus and/or calcium concentration. Participants'
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b'are not permitted to receive enzyme-inducing anti-epileptic drugs, including'
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b'carbamazepine, phenytoin, phenobarbital, and primidone.'
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b'Current use of coumarin-derived anticoagulant for treatment, prophylaxis or otherwise.'
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b'Therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed.'
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b'Have any known hypersensitivity to gemcitabine, cisplatin, calcium-lowering agents,'
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b'infigratinib, or their excipients.'
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b'Treatment with another investigational drug or other intervention within 30 days prior'
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b'to enrollment or within 5 half-lives of the investigational product, whichever is'
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b'longer.'
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b'Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star'
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b'fruits, pomelos, Seville oranges or products containing juice of these fruits within 7'
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b'days prior to first dose of study drug.'
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b'Have used medications known to prolong the QT interval and/or are associated with a'
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b'risk of Torsades de Pointes (TdP) 7 days prior to first dose of study drug.'
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b'Have used amiodarone within 90 days prior to first dose of study drug.'
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