Using ropidoxuridine to enhance radiation therapy for glioblastoma

Phase 2 Study of Ropidoxuridine as a Radiation Sensitizing Agent During Radiotherapy in Patients With Newly Diagnosed IDH-Wildtype Glioblastoma With Unmethylated MGMT Promoter

This study is testing if a new oral medication called ropidoxuridine can make radiation therapy more effective for patients with a specific type of brain cancer called glioblastoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shuttle Pharmaceuticals, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 6 sites (Washington, District of Columbia and 5 other locations)
• Trial ID: NCT06359379 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial evaluates the safety and efficacy of oral ropidoxuridine as a radiation-sensitizing agent in patients with newly diagnosed IDH-wildtype glioblastoma that has an unmethylated MGMT promoter. Participants will be randomly assigned to receive either 960 mg or 1200 mg of ropidoxuridine for 7 weeks, starting one week before standard radiotherapy. The study aims to determine the optimal dose of ropidoxuridine and assess its impact on treatment outcomes through MRI evaluations after the treatment period. The trial will also analyze pharmacokinetic, safety, and tolerability data to guide future treatment strategies.

Who should consider this trial

Good fit: Ideal candidates are adults with newly diagnosed IDH-wildtype glioblastoma and an unmethylated MGMT promoter who are eligible for standard radiotherapy.

Not a fit: Patients with prior radiation, electric field, or systemic therapy for glioblastoma may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve the effectiveness of radiation therapy for patients with glioblastoma, potentially leading to better survival rates.

How similar studies have performed: While the use of ropidoxuridine as a radiosensitizer is a novel approach, similar studies have shown promise in enhancing radiation therapy for various cancers.

Eligibility criteria

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.

Where this trial is running

Washington, District of Columbia and 5 other locations

• Lombardi Comprehensive Cancer Center — Washington, District of Columbia, United States (Recruiting)
• Miami Cancer Institute — Miami, Florida, United States (Recruiting)
• John Theurer Cancer Center at the Hackensack University Medical Center — Hackensack, New Jersey, United States (Recruiting)
• Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States (Recruiting)
• Allegheny General Hospital — Pittsburgh, Pennsylvania, United States (Recruiting)
• University of Virginia — Charlottesville, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Peter Dritschilo

Conditions Glioblastoma, IDH-wildtype; radiotherapy; radiation sensitizing agent; ropidoxuridine; unmethylated MGMT promoter