Trial Title:
Ropidoxuridine as a Radiosensitizer in Newly Diagnosed IDH-Wildtype Glioblastoma With Unmethylated MGMT Promoter
NCT ID:
NCT06359379
Condition:
Glioblastoma, IDH-wildtype
Conditions: Official terms:
Glioblastoma
Ropidoxuridine
Conditions: Keywords:
radiotherapy
radiation sensitizing agent
ropidoxuridine
unmethylated MGMT promoter
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ropidoxuridine
Description:
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.
Arm group label:
Ropidoxuridine 1200 mg
Arm group label:
Ropidoxuridine 960 mg
Other name:
5-iodo-2-pyrimidinone-2'-deoxyribose
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.
Detailed description:
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Lombardi Comprehensive Cancer Center
Address:
City:
Washington
Zip:
20007
Country:
United States
Status:
Recruiting
Contact:
Last name:
Matthew Witek, MD
Email:
Matthew.E.Witek@medstar.net
Investigator:
Last name:
Matthew Witek, MD
Email:
Principal Investigator
Facility:
Name:
Miami Cancer Institute
Address:
City:
Miami
Zip:
33176
Country:
United States
Status:
Recruiting
Contact:
Last name:
Robert Press, MD
Email:
robert.press@baptisthealth.net
Investigator:
Last name:
Robert Press, MD
Email:
Principal Investigator
Facility:
Name:
John Theurer Cancer Center at the Hackensack University Medical Center
Address:
City:
Hackensack
Zip:
07601
Country:
United States
Status:
Recruiting
Contact:
Last name:
Deric Park, MD, FACP
Email:
deric.park@hmhn.org
Investigator:
Last name:
Deric Park, MD, FACP
Email:
Principal Investigator
Facility:
Name:
Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Status:
Recruiting
Contact:
Last name:
Soma Sengupta, MD, PhD
Email:
ssengup@email.unc.edu
Investigator:
Last name:
Soma Sengupta, MD, PhD
Email:
Principal Investigator
Facility:
Name:
Allegheny General Hospital
Address:
City:
Pittsburgh
Zip:
15212
Country:
United States
Status:
Recruiting
Contact:
Last name:
Rodney Wegner, MD
Email:
rodney.wegner@ahn.org
Investigator:
Last name:
Rodney Wegner, MD
Email:
Principal Investigator
Facility:
Name:
University of Virginia
Address:
City:
Charlottesville
Zip:
22903
Country:
United States
Status:
Recruiting
Contact:
Last name:
David Schiff, MD
Email:
Ds4jd@uvahealth.org
Investigator:
Last name:
David Schiff, MD
Email:
Principal Investigator
Start date:
September 2, 2024
Completion date:
February 2027
Lead sponsor:
Agency:
Shuttle Pharmaceuticals, Inc.
Agency class:
Industry
Source:
Shuttle Pharmaceuticals, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06359379
