Randomized Phase II Trial to Evaluate the Efficacy of WSD0922-FU When Combined With Adjuvant Temozolomide in Patients With EGFR Mutant Glioblastoma
This phase II trial compares the effect of adding WSD0922-FU to temozolomide versus temozolomide alone in slowing disease progression in patients with Epidermal Growth Factor Receptor (EGFR)-mutant, IDH-wildtype glioblastoma. Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid and may kill tumor cells and slow down or stop tumor growth. WSD0922-FU is a targeted treatment which blocks EGFR. It is able to get into the brain and spinal cord and help treat those types of tumors. Adding WSD0922-FU to the usual treatment with temozolomide may be more effective in slowing disease progression, compared to temozolomide alone, in patients with EGFR-mutant, IDH-wildtype glioblastoma.
• Age \>= 18 years
• Histopathologic diagnosis of glioblastoma, IDH-wildtype \[as defined by the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors\] on primary pathology review
‣ NOTE: MGMT promoter methylation status must have been performed
• Glioblastomas must have a pathogenic EGFR mutation, with or without EGFR amplification, detected by Clinical Laboratory Improvement Act (CLIA)-certified next-generation sequencing
‣ EGFR mutation includes both deoxyribonucleic acid (DNA) sequence variants (e.g. point mutations, etc.) and transcript variants (e.g. EGFRvIII, etc.)
⁃ EXCEPTIONS: Glioblastomas which are EGFR wildtype with amplification are excluded. Glioblastomas which only have EGFR variants of unknown significance (without any pathogenic EGFR mutations) are also excluded
• Patients must have completed standard radiation (60 Gy in 30 fractions) with concurrent temozolomide (missing no more than 2 weeks of temozolomide), and adequately recovered from treatment related toxicities
‣ NOTE: Adjuvant temozolomide must not have been initiated
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Hemoglobin \> 9.0 g/dL (obtained =\< 14 days prior to registration)
• Leukocytes \> 3.0 x 10\^9/L (obtained =\< 14 days prior to registration)
• Absolute neutrophil count (ANC) \> 1.5 x 10\^9/L (obtained =\< 14 days prior to registration)
• Platelet count \> 100 x 10\^9/L (obtained =\< 14 days prior to registration)
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (\< 3 x ULN for patients with Gilbert's disease) (obtained =\< 14 days prior to registration)
• Alanine aminotransferase (ALT) and aspartate transaminase (AST) =\< 3 x ULN (obtained =\< 14 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =\< 14 days prior to registration)
• Calculated creatinine clearance \>= 45 mL/min using the Cockcroft-Gault formula (obtained =\< 14 days prior to registration)
• Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only
• Provide written informed consent
• Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
• Must be willing to take light-protective measures during the study and for two weeks after last dose of WSD0922-FU
• Willingness to provide mandatory tissue specimens for correlative research