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.
This is a randomized, open-label phase 2 study to assess the safety and efficacy of oral ropidoxuridine as a radiation sensitizing agent in patients with newly diagnosed wildtype isocitrate dehydrogenase glioblastoma with unmethylated O6-methylguanine-DNA methyltransferase promoter, receiving standard 60 Gy radiotherapy. In the dose optimization phase, a group of 40 patients will be evenly divided, with a 1:1 randomization, to receive ropidoxuridine for a duration of 7 weeks. They will be administered daily ropidoxuridine at two dose levels: either 960 mg or 1200 mg. This administration will occur 5 days a week, from Monday to Friday. Treatment with ropidoxuridine will start one week before radiotherapy (induction period) and continue concomitantly with 60 Gy standard radiotherapy fractionated in 2 Gy daily doses (Monday through Friday weeks 2 to 7, treatment period)), followed by a 4-week rest period. Following completion of this 11-week active study period, maintenance therapy, including temozolomide, tumor treating field device (Optune®), or other available treatment modalities, may be initiated at the discretion of the Investigator. Analysis of the pharmacokinetic, safety and tolerability data for the two cohorts will determine the optimal dose of ropidoxuridine, to be administered to the next cohort of 14 patients for determination of efficacy, compared to historical controls. A magnetic resonance imaging ( MRI) will be performed at the end of the active study period (Week 11). This MRI should not be used for disease assessment due to increased contrast enhancement in the acute radiation reaction phase, unless there is evidence of progression outside the radiotherapy fields. Radiographic disease assessment will be performed in accordance with community standard of care guidelines, every 3 months until disease progression. After the confirmed disease progression, survival monitoring follow-ups will occur every three months.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
Lombardi Comprehensive Cancer Center
Washington D.C., District of Columbia, United States
Miami Cancer Institute
Miami, Florida, United States
John Theurer Cancer Center at the Hackensack University Medical Center
Hackensack, New Jersey, United States
Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: he first 36 days of treatment.
Trough plasma concentration of orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily
Time frame: 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.
Time frame: The first 36 days of treatment.
Area under the curve for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.
Time frame: The first 36 days of treatment.
Half-life for orally administered ropidoxuridine, at dose levels of 960 and 1200 mg once daily.
Time frame: The first 36 days of treatment.
Overall survival at 12 months
Time frame: 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.
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Allegheny General Hospital
Pittsburgh, Pennsylvania, United States
University of Virginia
Charlottesville, Virginia, United States
Radiographic Response Rate
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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.
Overall Survival
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months.
Progression-Free Survival
Time frame: 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.
Six-Month Progression-Free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months.
Fraction of patients with tumor progression outside of the treatment area.
Time frame: 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.
Quantification of 9 relevant neurologic domains based on the NANO scale.
The Neurologic Assessment in Neuro-Oncology (NANO) scale is a clinical tool used to measure neurological function in patients with brain tumors. The scale can range from a score of 0 to a maximum score that depends on the severity and number of deficits. Higher scores on the NANO scale typically indicate a greater degree of neurological impairment.
Time frame: Measured from the time of study enrollment until 28 (±7) days following the completion of study treatment.