Ropidoxuridine + Whole Brain Radiation Therapy for Brain Metastasis

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

11 Participants Needed

Trial Summary

What is the purpose of this trial?

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 cancer that has spread to the brain (brain metastases). Ropidoxuridine may help whole brain radiation therapy work better by making cancer cells more sensitive to the radiation therapy.

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.

What data supports the effectiveness of the treatment Ropidoxuridine + Whole Brain Radiation Therapy for Brain Metastasis?

Research shows that hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) can help prevent cognitive decline while maintaining control over brain metastases, suggesting it may be a beneficial component of the treatment. ^{1 2 3 4 5}

Is Hippocampal Avoidance Whole-Brain Radiation Therapy (HA-WBRT) safe for humans?

Hippocampal Avoidance Whole-Brain Radiation Therapy (HA-WBRT) is designed to reduce the risk of memory and cognitive problems often seen with traditional whole-brain radiation therapy. Studies suggest that HA-WBRT can help preserve cognitive function while still effectively treating brain metastases. ^{2 3 4 6 7}

How does the treatment Ropidoxuridine + Whole Brain Radiation Therapy for Brain Metastasis differ from other treatments?

This treatment is unique because it combines Ropidoxuridine, a radiosensitizer that makes cancer cells more sensitive to radiation, with Whole-Brain Radiation Therapy (WBRT) that includes hippocampal avoidance to reduce cognitive side effects. This approach aims to improve tumor control while minimizing damage to areas of the brain responsible for memory and learning. ^{2 4 8 9 10}

Research Team

Pranshu Mohindra

Principal Investigator

Mayo Clinic Cancer Center LAO

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases: Local tumour control and survival. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) - a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG). [2021]

3. England pubmed.ncbi.nlm.nih.gov

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. [2023]

4. Poland 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. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Feasibility of hippocampal avoidance whole brain radiation in patients with hippocampal involvement: Data from a prospective study. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Hippocampal-Sparing Whole-Brain Radiotherapy for Lung Cancer. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy and chemotherapy of brain metastases. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Concurrent capecitabine and whole-brain radiotherapy for treatment of brain metastases in breast cancer patients. [2021]