Ropidoxuridine + Whole Brain Radiation Therapy for Brain Metastasis

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Lepto/pachy meningeal carcinomatosis, lymphoma/leukemia, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug ropidoxuridine can enhance the effectiveness of whole brain radiation therapy for individuals whose cancer has spread to the brain. The main goal is to determine the optimal dose of ropidoxuridine and its interaction with radiation treatment. The study seeks participants diagnosed with cancer that has metastasized to the brain and are scheduled for palliative whole brain radiation therapy. Individuals managing brain metastases without severe complications may be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it mentions that patients who have received certain treatments recently may not be eligible. It's best to discuss your specific medications with the trial team to see if they might affect your eligibility.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using ropidoxuridine with whole brain radiation therapy can cause side effects. In a study with 19 patients, side effects became more noticeable at a dose of 1800 mg per day. However, at a lower dose of 1200 mg per day, the treatment was easier to handle. Researchers recommend this lower dose for further study. This suggests that the treatment is more tolerable at lower doses, but monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ropidoxuridine is unique because it introduces a new active ingredient designed to enhance the effects of radiation therapy for brain metastases. Unlike standard treatments that typically rely solely on whole-brain radiotherapy, ropidoxuridine is taken orally and works by making cancer cells more sensitive to radiation. This combination could potentially improve outcomes by targeting tumors more effectively and reducing the overall duration of radiotherapy sessions. Researchers are excited about this approach because it might lead to better control of brain metastases with fewer side effects, offering new hope for patients.

What evidence suggests that ropidoxuridine combined with whole-brain radiation therapy could be effective for brain metastasis?

Research has shown that ropidoxuridine, administered alongside whole brain radiation therapy (WBRT) in this trial, might enhance WBRT's effectiveness for treating brain metastases. Ropidoxuridine increases cancer cells' sensitivity to radiation, potentially improving treatment outcomes. Studies have found that altering ropidoxuridine administration can affect its conversion into a tumor-targeting compound. Early trials in other cancers, such as glioblastoma, have begun and appear promising. Research on mice demonstrated that specific dosing schedules can enhance treatment efficacy without major side effects. These findings suggest that ropidoxuridine could potentially increase the success rate of radiation therapy in brain cancer patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Pranshu Mohindra

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with cancer that has spread to the brain. They must be in a stable condition, have good organ function, and not have had whole brain radiation before. People with primary germ cell tumors or leukemia/lymphoma, pregnant women, those on high-dose steroids or recent chemotherapy are excluded.

Inclusion Criteria

My kidneys are functioning well enough (creatinine clearance rate is good).

Ability to understand and the willingness to sign a written informed consent document

I am HIV positive with a CD4 count of 250 or higher and on anti-viral therapy.

Exclusion Criteria

I need more than 8 mg of dexamethasone daily before starting whole brain radiation therapy.

I do not have any severe illnesses that could worsen due to the study or prevent me from following the study requirements.

I have severe brain complications due to cancer spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ropidoxuridine orally once daily for 28 days and undergo whole brain radiation therapy starting on day 8 for a total of 15 fractions

4 weeks

Daily visits for radiation therapy, oral medication taken at home

Follow-up

Participants are monitored for safety, effectiveness, and delayed neurological toxicity after treatment

Up to 2 years

Every 2 months for 6 months, then every 3-4 months for 6 months, and every 6 months for 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ropidoxuridine
• Whole-Brain Radiotherapy

Trial Overview

The study is testing ropidoxuridine combined with whole brain radiation therapy (WBRT) to see if it improves treatment outcomes for brain metastases. It aims to find the safest dose of ropidoxuridine that works best alongside WBRT.

How Is the Trial Designed?

Group I: Treatment (ropidoxuridine, WBRT) Experimental Treatment 5 Interventions

Patients receive ropidoxuridine PO QD on days 1-28 and undergo WBRT daily for not more than 5 days per week beginning on day 8 for a total of 15 fractions in the absence of disease progression or unacceptable toxicity.

Whole-Brain Radiotherapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Approved in United States as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Approved in Canada as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Approved in Japan as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Approved in China as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Approved in Switzerland as Whole-Brain Radiation Therapy for:

• Brain metastases
• Primary brain tumors
• Small cell lung cancer with brain metastases

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 518 patients with brain metastases, those who survived 4 months or longer showed a significant reduction in neurocognitive function failure (NCFF) when treated with hippocampal avoidant whole brain radiotherapy (HA-WBRT) compared to standard WBRT.

Patients with lower baseline cognitive impairment (as measured by the MD Anderson Symptom Inventory-Brain Tumor scores) and those with primary lung tumors experienced greater neuroprotective benefits from HA-WBRT, highlighting the importance of individual patient characteristics in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. Cherng, HR., Sun, K., Bentzen, S., et al.[2023]

The review discusses various treatment options for newly diagnosed and recurrent brain metastases, including whole-brain radiotherapy, radiosurgery, and chemotherapy, highlighting the importance of tailoring treatments to specific patient prognostic subgroups.

Emerging therapies, such as new radiosensitizers and cytotoxic agents, are being explored to improve local control and survival rates while managing the risk of late neurotoxicity associated with these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy of brain metastases. Soffietti, R., Costanza, A., Laguzzi, E., et al.[2018]

Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) effectively preserves neurocognitive function in patients with brain metastasis, showing a significant decrease in cognitive decline over 12 months after treatment.

Patients treated with HA-WBRT also experienced improvements in quality of life, particularly in social well-being, indicating that this treatment not only controls disease but also enhances overall patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal avoidance whole brain radiotherapy in brain metastasis using volumetric modulated arc therapy: experience from a Regional Cancer Centre of Eastern India. Deepsikha, G., Maji, T., Lahiri, D., et al.[2023]

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) combined with a simultaneous integrated boost (SIB) showed a local tumor control rate of 73% and a median intracranial progression-free survival of 40 weeks in a study of 20 patients.

The treatment was found to be safe, with no significant acute or late toxicities observed, suggesting it may help prevent cognitive decline associated with standard whole brain radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival. Oehlke, O., Wucherpfennig, D., Fels, F., et al.[2022]

TomoTherapy is the most effective method for Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT), providing a significantly better dose distribution compared to IMRT and RapidArc, as indicated by a superior homogeneity index.

RapidArc, while not as effective in dose distribution as TomoTherapy, offers the fastest treatment delivery time, making it a suitable alternative when time efficiency is a priority.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. Rong, Y., Evans, J., Xu-Welliver, M., et al.[2022]

Whole-brain radiotherapy (WBRT) is a common treatment for lung cancer patients with brain metastases, but it can lead to cognitive decline due to radiation damage to the hippocampus.

Hippocampal-sparing WBRT is a promising technique that aims to reduce cognitive side effects while still effectively treating brain metastases, supported by both preclinical and clinical evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer. Zhao, R., Kong, W., Shang, J., et al.[2022]

Citations

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clinicaltrials.gov

clinicaltrials.gov/study/NCT02993146

Ropidoxuridine and Whole Brain Radiation Therapy in ...

Ropidoxuridine may help whole brain radiation therapy work better by making cancer cells more sensitive to the radiation therapy. Detailed Description. PRIMARY ...

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Schedule-Dependent Drug Effects of Oral 5-Iodo-2 ...

We show that these alternative dosing schedules can improve the efficiency of IPdR conversion to IUdR, which subsequently affect the degree of tumor ...

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clinicaltrials.gov/study/NCT02381561?intr=ROPIDOXURIDINE&aggFilters=studyType:int&viewType=Table&rank=3

Ropidoxuridine in Treating Patients With Advanced ...

This phase I trial studies the side effects and best dose of ropidoxuridine in treating patients with gastrointestinal cancer that has ...

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curetoday.com

curetoday.com/view/first-patients-dosed-in-phase-2-trial-of-ropidoxuridine-for-glioblastoma

First Patients Dosed in Phase 2 Trial of Ropidoxuridine for ...

The first three patients with glioblastoma have begun treatment with ropidoxuridine in a phase 2 clinical trial for a new brain cancer treatment ...

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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 conclude that a 14-day po schedule of IPdR at up to 1500 mg/kg/day results in no significant systemic toxicity in athymic mice and is associated with ...

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

Phase I and Pharmacology study of Ropidoxuridine (IPdR) ...

Nineteen patients were entered on study. Dose limiting toxicity was encountered at 1800mg QD, and the recommended Phase II dose is 1200mg QD.

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clinicaltrials.gov/study/NCT02993146?tab=history&a=84

Record History | ver. 84: 2024-01-25 | NCT02993146

This phase I trial studies the side effects and best dose of ropidoxuridine when given together with whole brain radiation therapy in treating patients with ...

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researchgate.net

researchgate.net/publication/13731847_Preclinical_evaluation_of_5-iodo-2-pyrimidinone-2'-deoxyribose_as_a_prodrug_for_5-iodo-2'-deoxyuridine-mediated_radiosensitization_in_mouse_and_human_tissues

(PDF) Preclinical evaluation of 5-iodo-2-pyrimidinone-2

Here, we further evaluate IPdR metabolism, systemic toxicity, and percentage DNA incorporation in athymic mouse normal tissues and a human colon ...

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clinicaltrials.gov/study/NCT02993146?tab=history&a=58

Record History | ver. 58: 2019-12-23 | NCT02993146

To conduct a phase 1 dose escalation trial in patients with brain metastases to determine the maximum tolerated dose (MTD) of ropidoxuridine (5-iodo-2- ...