Ropidoxuridine as a Radiosensitizer in Newly Diagnosed IDH-Wildtype Glioblastoma With Unmethylated MGMT Promoter

Inclusion Criteria:

* Written informed consent form signed and dated by patient or legally authorized representative according to local guidelines, prior to the performance of any study-specific procedures, sampling, or analyses. Participants with impaired decision-making capacity must have a close caregiver or legally authorized representative present.
* Histologically confirmed supratentorial glioblastoma isocitrate dehydrogenase (IDH) wild-type classification (2021 World Health Organization Classification of Tumours, 5th Edition, Volume 6) with unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter (defined as MGMT methylation status ≤20% by pyrosequencing, and no prior radiation, electric field, or systemic therapy. Glucocorticoid therapy for symptom control is allowed.
* Patients should, in the opinion of the investigator, be candidates for 60 Gy radiotherapy in 2 Gy fractions over 6 weeks, per standard of care. Hypofractionated radiotherapy schedules (e.g., 36 Gy in 3 Gy fractions) are not allowed.
* Eastern Cooperative Oncology Group performance status of 0, 1 or 2.
* Adequate renal, liver and bone marrow function:

  * Hemoglobin \>9.0 g/dL
  * Absolute neutrophil count \>1.5 × 10\^9/L
  * Platelet count \>100 × 10\^9/L
  * Total bilirubin ≤1.5 × upper limit of normal (ULN), unless due to documented Gilbert's disease (≤3 × ULN)
  * Aspartate aminotransferase / alanine aminotransferase ≤4×ULN
  * Creatinine clearance ≥60 mL/min calculated as per Cockcroft-Gault equation.
* Life expectancy ≥12 weeks.
* Have recovered from the immediate post-operative period and is maintained on a stable corticosteroid regimen (no increase for 5 days) prior to initiation of study treatment.
* Female patients, of childbearing potential, must have a negative serum pregnancy test within 7 days prior to taking study medication and agree to use at least one highly effective form of contraception during study treatment and for at least 120 days after the last dose of study treatment.
* Male patients must agree to use an adequate method of contraception from enrollment through 120 days after the last dose of study treatment.

Exclusion Criteria:

* Any prior treatment for glioblastoma, including chemotherapy, immunotherapy, targeted therapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, lymphokine-activated killer cell therapy or gene therapy), or radiotherapy. Glucocorticoid therapy is permitted.
* Second primary malignancy expected to require active treatment within a 6-month period (except basal cell or early-stage squamous cell carcinoma of the skin that may be excised). Patients who had another malignancy in the past but have been free of active disease for more than 1 year, are eligible even if under active surveillance, at the discretion of the Investigator. Adjuvant anti hormonal treatment for prior breast or prostate cancer is allowed, but no other concomitant anticancer treatment.
* Any investigational therapy (for any concomitant condition) within 28 days or within 5 half-lives of study entry (whichever is shorter).
* Use of acid-reducing agents including proton pump inhibitors and histamine-2 blockers.
* Inability to comply with protocol or study procedures.
* Women who are pregnant or breastfeeding.
* Inability to swallow oral medication or gastrointestinal disorder expected to severely affect drug absorption (e.g., short bowel syndrome).
* Ongoing bacterial, viral, or fungal infection requiring systemic therapy. Prophylactic therapy is allowed. Patients with a history of Human Immunodeficiency Virus, Hepatitis B virus, Hepatitis C virus infection are allowed if treated with effective anti-viral therapy that results in undetectable viral load.
* Any medical condition, which in the opinion of the Investigator, places the patient at an unacceptably high risk for toxicities, or makes the patient unsuitable for study participation.