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

NCT06359379 | Terminated Phase 2 FDA Drug

• 1 other identifier: S22-11168
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

This is a randomized, open-label, phase 2 study evaluating the safety and efficacy of oral ropidoxuridine as a radiation-sensitizing agent in patients with newly diagnosed wild-type isocitrate dehydrogenase glioblastoma with an unmethylated O6-methylguanine-DNA methyltransferase promoter, undergoing standard 60 Gy radiotherapy.

Conditions

Glioblastoma, IDH-wildtype

Keywords

radiotherapy; radiation sensitizing agent; ropidoxuridine; unmethylated MGMT promoter

Outcome Measures

Primary Outcomes (7)

• Number of patients treated with oral ropidoxuridine at dose levels of 960 and 1200 mg once daily, with treatment-related adverse events assessed by CTCAE v5.0.

  From the first day of treatment start until 30 days after treatment completion

• adiographic response rate, disease control rate, best overall response, and duration of overall response in patients treated with oral ropidoxuridine at 960 and 1200 mg daily doses, assessed using the Response Assessment in Neuro-Oncology criteria.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Maximum plasma concentration for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.

  he first 36 days of treatment.

• Trough plasma concentration of orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily

  The first 36 days of treatment.

• Time to maximum plasma concentration for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.

  The first 36 days of treatment.

• Area under the curve for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.

  The first 36 days of treatment.

• Half-life for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.

  The first 36 days of treatment.

Secondary Outcomes (10)

• Overall survival at 12 months

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months.

• Radiographic Response Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Disease Control Rate

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Best Overall Response

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

• Duration of Response

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months.

Study Arms (2)

Ropidoxuridine 960 mg

EXPERIMENTAL

Ropidoxuridine is administered orally at 960 mg, 5 days a week for a total of 7 weeks, starting 1 week before the initiation of radiotherapy.

Drug: Ropidoxuridine

Ropidoxuridine 1200 mg

EXPERIMENTAL

Ropidoxuridine is administered orally at 1200 mg, 5 days a week for a total of 7 weeks, starting 1 week before the initiation of radiotherapy.

Drug: Ropidoxuridine

Interventions

Ropidoxuridine DRUG

Ropidoxuridine is administered daily, 5 days a week, for 7 weeks, starting one week prior to radiotherapy, and then concurrently with a standard 60 Gy radiotherapy, followed by a 4-week rest period.

Also known as: 5-iodo-2-pyrimidinone-2'-deoxyribose

Ropidoxuridine 1200 mg; Ropidoxuridine 960 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shuttle Pharmaceuticals, Inc.: lead

Study Sites (6)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

John Theurer Cancer Center at the Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

ropidoxuridine

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2024
• First Posted: April 11, 2024
• Study Start: September 2, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 18, 2025

Record last verified: 2025-12

Locations

US (6)