Overview

The purpose of this study is to test WSD0628 in combination with radiation therapy for recurrent brain tumors.

Eligibility

Inclusion Criteria:

• Age ≥18 years
• Histological confirmation of one of the following:
• Glioblastoma, IDH-wildtype
• Grade 3 or 4 IDH1/2 mutant astrocytoma (2021 WHO classification)
• Measurable disease as defined in Section 11.0
• Disease progression after previous treatment for glioma with radiation and chemotherapy
• Minimum life expectancy of at least 3 months
• Group C only: Dose Expansion, Brain Tumor Penetration Group: plan for radiosurgery and surgical resection as part of routine clinical care
• ECOG Performance Status (PS) 0, 1 or 2 (Appendix I)
• The following laboratory values obtained ≤15 days prior to registration:
  • Hemoglobin ≥9.0 g/dL
  • Leukocytes ≥3.0 x 109/L
  • Absolute neutrophil count (ANC) ≥1500/mm3 or 1.5 x 109/L
  • Platelet count ≥100,000/mm3 or 100 x 109/L
  • Total bilirubin ≤1.5 x ULN and <3 mg/dL for patients with Gilbert's disease
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤3 x ULN
  • PT/INR/aPTT ≤1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy
• Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula below:

        Creatinine clearance for males = (140-age)(weight in kg)(72)(serum creatinine inmgdL⁄)
        Creatinine clearance for females = (140-age)(weight in kg)(0.85)(72)(serum creatinine
        inmgdL⁄)
          -  Negative pregnancy test done ≤7 days prior to registration, for persons of
             childbearing potential only
          -  Willing to take light-protective measures during the study and for two weeks after
             their last dose of WSD0628
          -  Provide written informed consent
          -  Willing to return to enrolling institution for follow-up (during the Active Monitoring
             Phase of the study)
          -  Willingness to provide mandatory tissue specimens for correlative research (see
             Section 17.0)
        Exclusion Criteria:
          -  Any of the following because this study involves an investigational agent, the
             genotoxic, mutagenic, and teratogenic effects of which on the developing fetus and
             newborn are unknown:
               -  Pregnant persons
               -  Nursing persons
               -  Persons of childbearing potential and persons able to father a child who are
                  unwilling to employ adequate contraception
          -  Uncontrolled intercurrent illness including, but not limited to:
               -  ongoing or active infection
               -  symptomatic congestive heart failure
               -  unstable angina pectoris
               -  cardiac arrhythmia
               -  or psychiatric illness/social situations that would limit compliance with study
                  requirements
        Any of the following cardiac criteria:
          -  Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc
             interval >480 milliseconds (ms) (CTCAE Grade 1) using Fredericia's QT correction
             formula.
          -  History of additional risk factors for Torsades de Pointes (e.g., heart failure,
             hypokalemia, family history of Long QT. Syndrome).
          -  Use of concomitant medications that prolong the QT/QTc interval
          -  History of myocardial infarction ≤6 months prior to registration, or congestive heart
             failure requiring use of ongoing maintenance therapy for life-threatening ventricular
             arrhythmias
               -  Known coagulopathy increasing the risk of bleeding or history of clinically
                  significant hemorrhage, including significant intracranial tumor related
                  hemorrhage
               -  Any of the following medications:
          -  Enzyme-inducing anticonvulsants within two weeks of enrollment NOTE: Patients can be
             enrolled after a change to non-enzyme inducing anticonvulsants)
          -  Patients taking more than 8 mg of dexamethasone per day (or equivalent steroid dose)
             at time of enrollment
               -  Any of the following prior therapies:
          -  Radiation therapy less than 26 weeks prior to registration
          -  Chemotherapy, immunotherapy, bevacizumab or any investigational drug within four
             weeks, or carmustine (CCNU) or lomustine (BCNU) within six weeks prior to registration
               -  Past medical history of interstitial lung disease, drug-induced interstitial lung
                  disease, radiation pneumonitis which required steroid treatment, or any evidence
                  of clinically active interstitial lung disease
               -  History of hypersensitivity to active or inactive excipients of WSD0628 or drugs
                  with a similar chemical structure or class to WSD0628
               -  Refractory nausea and vomiting if not controlled by supportive therapy, chronic
                  gastrointestinal diseases, inability to swallow the formulated product or
                  previous significant bowel resection that would preclude adequate absorption of
                  WSD0628
               -  Uncontrolled hypertension
               -  History of severe brain-injury or stroke
               -  Receiving any other investigational agent which would be considered as a
                  treatment for the primary neoplasm