Ropidoxuridine for Glioblastoma

Recruiting at 9 trial locations

Overseen By Peter Dritschilo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Shuttle Pharmaceuticals, Inc.

Must not be taking: Acid-reducing agents

Disqualifiers: Prior glioblastoma treatment, Second malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

Duration: 6 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ropidoxuridine for glioblastoma, a type of brain cancer. The goal is to determine if this medication can enhance the effectiveness of radiation therapy. Participants will receive varying doses of ropidoxuridine alongside standard radiation therapy to identify the most effective combination. Individuals with newly diagnosed glioblastoma, who have not yet begun treatment and have a specific tumor profile (IDH wild-type with unmethylated MGMT promoter), may be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does prohibit the use of acid-reducing agents like proton pump inhibitors and histamine-2 blockers. Glucocorticoid therapy for symptom control is allowed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ropidoxuridine underwent testing in early animal studies. In one study, mice tolerated high doses of up to 1500 mg/kg/day without significant harmful effects, suggesting the drug was well-tolerated in animals.

Currently, this trial is in the early stages of human testing, meaning there is limited information about its safety in people so far. However, its progression to human trials indicates promise in earlier animal studies.

In this trial, two doses are being tested: 960 mg and 1200 mg. Participants take these doses orally, five days a week, for seven weeks. As this is an early-phase study, researchers closely monitor for any side effects to ensure the treatment's safety while learning more about its effects on humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Researchers are excited about Ropidoxuridine for glioblastoma because it offers a novel approach to treatment. Unlike the standard therapies like temozolomide, which primarily act by interfering with cancer cell DNA replication, Ropidoxuridine is a radiosensitizer, meaning it enhances the effectiveness of radiotherapy by making cancer cells more susceptible to radiation damage. This could potentially improve treatment outcomes by targeting tumor cells more precisely. Additionally, the oral administration of Ropidoxuridine at specific doses (960 mg and 1200 mg) provides a flexible and potentially more convenient treatment regimen compared to some existing intravenous options.

What evidence suggests that ropidoxuridine could be an effective treatment for glioblastoma?

Research has shown that Ropidoxuridine, also known as IPdR, may enhance the effectiveness of radiation therapy in treating glioblastoma. Studies using human glioblastoma models found that IPdR caused tumors to shrink more as the dose increased when combined with radiation. Earlier trials demonstrated that adding IPdR to radiation therapy slowed tumor growth and improved treatment outcomes. In this trial, participants will receive either 960 mg or 1200 mg of Ropidoxuridine orally to evaluate its effectiveness alongside radiation therapy. These findings suggest that Ropidoxuridine could be a valuable component of glioblastoma treatment, particularly for patients undergoing radiation therapy. Overall, early results indicate that Ropidoxuridine is a promising option for enhancing the effects of radiation therapy in glioblastoma patients. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with a new diagnosis of IDH-wildtype glioblastoma, which is an aggressive brain cancer, and their tumors must have an unmethylated MGMT promoter. Participants should be ready to undergo standard radiotherapy.

Inclusion Criteria

My kidney, liver, and bone marrow are functioning well.

I can care for myself and am up and about more than 50% of my waking hours.

I have signed the consent form or my legal representative has.

Exclusion Criteria

Any investigational therapy within 28 days or within 5 half-lives of study entry.

I am not pregnant or breastfeeding.

Any medical condition that places the patient at an unacceptably high risk for toxicities, or makes the patient unsuitable for study participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive ropidoxuridine for 1 week before starting radiotherapy

1 week

5 visits (in-person)

Treatment

Participants receive ropidoxuridine and 60 Gy radiotherapy over 6 weeks

6 weeks

30 visits (in-person)

Rest

Participants undergo a 4-week rest period following treatment

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRI at week 11 and radiographic assessments every 3 months

Ongoing

Every 3 months until disease progression

What Are the Treatments Tested in This Trial?

Interventions

• Ropidoxuridine

Trial Overview The study tests ropidoxuridine's effectiveness in making tumor cells more sensitive to radiation therapy. It's a phase 2 trial where patients receive either the usual treatment or the same plus oral ropidoxuridine.

How Is the Trial Designed?

Group I: Ropidoxuridine 960 mg Experimental Treatment 1 Intervention

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.

Group II: Ropidoxuridine 1200 mg Experimental Treatment 1 Intervention

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.

Ropidoxuridine is already approved in United States for the following indications:

Approved in United States as Ropidoxuridine for:

• Glioblastoma

Who Is Running the Clinical Trial?

Shuttle Pharmaceuticals, Inc.

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

Oral administration of the prodrug IPdR significantly increased the incorporation of IUdR into DNA in MMR-deficient colon cancer xenografts compared to MMR-proficient ones, indicating a potential mechanism for enhanced radiosensitization.

IPdR treatment led to substantial radiosensitization in both MMR-deficient and MMR-proficient tumors, with a greater sensitization effect observed in MMR-deficient tumors, while showing no significant systemic toxicity during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential radiosensitization in DNA mismatch repair-proficient and -deficient human colon cancer xenografts with 5-iodo-2-pyrimidinone-2'-deoxyribose. Seo, Y., Yan, T., Schupp, JE., et al.[2020]

A 14-day oral administration of 5-iodo2-pyrimidinone-2'-deoxyribose (IPdR) at doses up to 1500 mg/kg/day showed no significant systemic toxicity in athymic mice, indicating its safety for further clinical trials.

IPdR significantly enhanced the incorporation of the active drug IUdR into tumor DNA and improved radiosensitization in glioblastoma xenografts compared to radiation therapy alone, suggesting its potential efficacy in treating high-grade gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical toxicity and efficacy study of a 14-day schedule of oral 5-iodo-2-pyrimidinone-2'-deoxyribose as a prodrug for 5-iodo-2'-deoxyuridine radiosensitization in U251 human glioblastoma xenografts. Kinsella, TJ., Vielhuber, KA., Kunugi, KA., et al.[2020]

The study found that administering the drug IPdR three times a day (t.i.d.) significantly improved its conversion to the active form IUdR, leading to better incorporation of IUdR into tumor DNA and enhanced tumor growth delay compared to a once daily (q.d.) schedule.

The every other day (q.o.d.) dosing schedule also showed improved conversion efficiency and resulted in less systemic toxicity, making it a promising option for future clinical trials in enhancing tumor radiosensitization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schedule-dependent drug effects of oral 5-iodo-2-pyrimidinone-2'-deoxyribose as an in vivo radiosensitizer in U251 human glioblastoma xenografts. Seo, Y., Yan, T., Schupp, JE., et al.[2020]

The study found that combining the radiosensitizer 5-bromo-2-doxyuridine (BrdUrd) with continuous low dose rate irradiation significantly enhances the effectiveness of treatment for malignant glioma, particularly at a dose rate of 12 cGy/hr.

The results suggest that BrdUrd can improve the efficacy of both temporary and permanent radiation implants, making it a promising option for enhancing glioma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Halogenated pyrimidine sensitization of low dose rate irradiation in human malignant glioma. McLaughlin, PW., Mancini, WR., Stetson, PL., et al.[2019]

In a study of 60 patients with high-grade gliomas, including glioblastoma multiforme, the combination of halogenated pyrimidines and high-dose brain irradiation resulted in a median survival of 13 months, with 24% of patients surviving 18 months.

Patients who completed the planned treatment had a better median survival of 14 months and a 30% 18-month survival rate, indicating that the treatment regimen may be effective and comparable to other therapies for glioblastoma multiforme.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Halogenated pyrimidines as radiosensitizers in the treatment of glioblastoma multiforme. Jackson, D., Kinsella, T., Rowland, J., et al.[2019]

Orally administered 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR) is efficiently converted to 5-iodo-2'-deoxyuridine (IUdR) in athymic mice, showing minimal toxicity even at high doses (up to 2 g/kg) over 6 days, which is a significant improvement over continuous infusion of IUdR that caused over 20% body weight loss.

IPdR not only enhances the incorporation of IUdR into DNA of tumor cells but also improves the radiation response of human colon cancer xenografts, suggesting its potential as a prodrug for radiosensitization in resistant cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of 5-iodo-2-pyrimidinone-2'-deoxyribose as a prodrug for 5-iodo-2'-deoxyuridine-mediated radiosensitization in mouse and human tissues. Kinsella, TJ., Kunugi, KA., Vielhuber, KA., et al.[2020]

In a phase I clinical trial involving 19 patients with advanced metastatic gastrointestinal cancers, the oral prodrug IPdR was found to be feasible and tolerable when administered daily for 28 days alongside radiation therapy, with a recommended dose of 1,200 mg per day.

Pharmacokinetic studies showed that IPdR achieved plasma levels of IUdR that are effective for radiosensitization, leading to significant treatment responses, including 2 complete responses and 3 partial responses in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and Pharmacology Study of Ropidoxuridine (IPdR) as Prodrug for Iododeoxyuridine-Mediated Tumor Radiosensitization in Advanced GI Cancer Undergoing Radiation. Kinsella, T., Safran, H., Wiersma, S., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2128756/

5-iodo-2-pyrimidinone-2′-deoxyribose (IPdR)-mediated ... In this study, we demonstrate IPdR dose-dependent tumor cytotoxicity and radiosensitization in U87 human glioblastoma sc xenografts using analyses of tumor ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6801071/

Phase I and Pharmacology study of Ropidoxuridine (IPdR) ... We report the clinical and pharmacologic results of a first-in-human phase I dose escalation study of IPdR + concurrent radiation therapy (RT)

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301607038679

5-Iodo-2-Pyrimidinone-2′-Deoxyribose–Mediated ... In the present study, we report effective IPdR dose-related radiosensitization, with modest tumor growth delay using higher doses of p.o. IPdR alone and modest ...

4. aacrjournals.org aacrjournals.org/clincancerres/article/6/4/1468/288141/Preclinical-Toxicity-and-Efficacy-Study-of-a-14

Preclinical Toxicity and Efficacy Study of a 14-day Schedule of ... We also found an improvement in the therapeutic gain with p.o. IPdR for 14 days compared to continuous infusion IUdR for 14 days with a≥2-fold increase in the ...

5. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/ropidoxuridine-shows-promise-in-glioblastoma-trial/

Ropidoxuridine Shows Promise in Glioblastoma Trial Positive results from this trial could establish IPdR as a crucial component in glioblastoma treatment, particularly for this patient subgroup.

6. withpower.com withpower.com/trial/phase-2-glioblastoma-idh-wildtype-5-2024-0a6a5

Ropidoxuridine for Glioblastoma 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 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06359379?intr=ROPIDOXURIDINE&aggFilters=studyType:int&viewType=Table&rank=1

Study Details | NCT06359379 | Ropidoxuridine as a ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...