A Surgical Window of Opportunity Clinical Trial of Troriluzole in Recurrent IDH Wild-Type Glioblastoma

Exclusion Criteria

• •Laboratory values at the Screening Visit:
• •* ANC count \< 1,500/mm3; growth-factor support within 7 days for filgrastim or other short acting biosimilars or 21 days for pegfilgrastim or other long acting biosimilars to increase the ANC is not allowed.
• •* Platelets \<100,000/mm3;
• •* Hemoglobin \< 9 g/dL;
• •* Total bilirubin \> 2 × the upper limit of normal (ULN) (unless subject has documented history of Gilbert's Syndrome in which case subject may be enrolled if total bilirubin is less than 5 mg/dL, assuming all other criteria are fulfilled);
• •* Aspartate aminotransferase (AST \[SGOT\]) \> 1.5 x ULN;
• •* Alanine aminotransferase (ALT \[SGPT\]) \> 1.5 x ULN;
• •* Serum creatinine \> 1.5 mg/dL or a calculated creatinine clearance \< 60 mL/min; and
• •* Positive serum β-hCG test in any individual assigned female at birth and is of childbearing potential (defined as ≤ 50 years of age, or \> 50 years of age with a history of amenorrhea for ≤12 months prior to study entry).
• •Has presence of diffuse leptomeningeal disease or extracranial disease.
• •Prior treatment with troriluzole or riluzole
• •From study treatment initiation, treatment with temozolomide less than 23 days, treatment with CCNU or BCNU less than 42 days, treatment with anti-VEGF therapy such as bevacizumab less than 6 months, or treatment with any cancer-directed systemic therapy less than 4 weeks or 5 half-lives, whichever is shorter. No wash-out period is required from tumor treating fields (TTF).
• •Use of any investigational agents within 28 days of baseline or 5 half-lives from study initiation, whichever is shorter.
• •Radiotherapy within 12 weeks prior to registration unless new enhancement is outside the radiation field (beyond the high-dose region of 80% isodense line) or evidence of viable tumor on histopathologic sampling.
• •Presence of a clinically significant allergy, hypersensitivity, or toxicity of prior therapy, with the exception of alopecia or lymphopenia, that has not resolved to ≤ Grade 1 or pre-treatment baseline, as determined by National Cancer Institute CTCAE v 5.0.
• •Major surgery within 28 days prior to initiation of study drug.
• •Active or clinically unstable bacterial, viral, or fungal infection requiring systemic therapy.
• •Any contraindication to MRI examination.
• •Requires medications that are known to be strong inhibitors or inducers of CYP1A2 enzymes or anti-glutamergic agents (e.g., perampanel) or hepatotoxic drugs which may increase the risk of hepatotoxicity (e.g., allopurinol, methyldopa, sulfasalazine). A washout of 10 days or 5 half-lives, whichever is shorter, is required prior to study treatment initiation. Oral contraceptives which contain ethinyl estradiol (moderate CYP1A2 inhibitor) are allowed.
• •Pregnant or lactating female.
• •History of interstitial lung disease.
• •Known history of hepatitis B, human immunodeficiency virus (HIV), or active hepatitis C infection requiring treatment with antiviral therapy. NOTE: HIV testing is not required in the absence of clinical suspicion.
• •Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the Investigator's opinion, would make the subject inappropriate for entry into this study.
• •Difficulty swallowing or malabsorption syndrome; refractory nausea and vomiting, chronic gastrointestinal (GI) disease or previous significant bowel resection with clinically significant sequelae that would preclude adequate absorption of study drug.