PRDR WBRT for Brain Cancer

Recruiting at 1 trial location

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: NMDA antagonists

Disqualifiers: Hematological malignancy, Leptomeningeal metastases, Dementia, 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 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks for WBRT, up to 24 weeks for Memantine

53 Participants Needed

Trial Summary

What is the purpose of this trial?

Study patients will receive Whole-brain radiation therapy (WBRT) - pulsed reduced dose rate (PRDR) within 14 days of registration. All patients will receive single daily fractions using 3D conformal radiotherapy. A dose of 30 Gy in 10 fractions will be delivered using the PRDR technique.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are taking memantine or other NMDA antagonists, you may need to stop, as these are contraindicated.

What data supports the effectiveness of the treatment WBRT for brain cancer?

Whole Brain Radiation Therapy (WBRT) is commonly used to manage brain metastases (cancer spread to the brain) and can help control symptoms. It is often used after surgery to improve local control of the disease, especially in patients whose cancer outside the brain is under control. ^{1 2 3 4 5}

Is whole-brain radiation therapy (WBRT) safe for humans?

Whole-brain radiation therapy (WBRT) is generally considered safe, but it can have side effects. Early side effects are usually mild, but late complications can affect brain function and quality of life. Research is ongoing to reduce these risks, such as using techniques to protect certain brain areas. ^{3 4 6 7 8}

How is the treatment WBRT for brain cancer different from other treatments?

Whole Brain Radiation Therapy (WBRT) is unique because it targets the entire brain to control symptoms in patients with brain metastases, unlike other treatments that may focus on specific areas to avoid side effects. It is often used when there are multiple metastases or after surgery to reduce the chance of cancer returning, but it may not improve overall survival. ^{1 2 3 9 10}

Research Team

Lindsay Puckett, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for adults over 18 with brain metastases from solid tumors, expected to live more than six months. They must have a good performance status, be able to do neurocognitive tests, and start treatment within two weeks of joining. Prior treatments are okay except whole brain radiation. Pregnant women or those not using contraception, non-English speakers, and patients with certain medical conditions are excluded.

Inclusion Criteria

Creatinine clearance is ≥ 30 mL/min

I have had treatment that affects my whole body.

I was 18 or older when my brain cancer was diagnosed.

Exclusion Criteria

Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician, prevent informed consent or completion of protocol treatment, and/or follow-up visits

I have had whole brain radiation therapy before.

Women of childbearing potential who are known to be pregnant or are unwilling to use an acceptable method of contraception from the time of informed consent until completion of the course of radiotherapy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive Whole-brain radiation therapy (WBRT) using the pulsed reduced dose rate (PRDR) technique, with a dose of 30 Gy in 10 fractions. Memantine is administered starting one to two days prior to WBRT and continues for up to 24 weeks.

2 weeks for WBRT, up to 24 weeks for Memantine

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on neurocognitive outcomes and clinical patient outcomes associated with radiation treatment of brain metastases.

4 weeks

Treatment Details

Interventions

• WBRT

Trial Overview The study tests Whole-brain radiation therapy (WBRT) using a Pulsed Reduced Dose-Rate (PRDR) technique alongside Memantine medication. Patients will receive daily WBRT sessions in ten fractions totaling 30 Gy via the PRDR method to optimize neurocognition in brain tumor treatment.

Participant Groups

Group I: WBRT-PRDR plus memantine. Experimental Treatment 2 Interventions

Study patients will receive WBRT-PRDR within 14 days of registration. All patients will receive single daily fractions using 3D conformal radiotherapy. A dose of 30 Gy in 10 fractions will be delivered using the PRDR technique. Memantine should ideally start two days (or one day) prior to WBRT PRDR and must start no later than the fourth WBRT PRDR treatment and will continue for a maximum of 24 weeks (≈six months). Memantine will be administered as per standard institutional guidelines.

WBRT is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Whole Brain Radiation Therapy for:

• Brain metastases
• Cancer treatment

Approved in European Union as Whole-Brain Radiotherapy for:

• Brain metastases
• Cancer treatment

Approved in Canada as WBRT for:

• Brain metastases
• Cancer treatment

Approved in Japan as Whole Brain Radiation Therapy for:

• Brain metastases
• Cancer treatment

Approved in China as Whole-Brain Radiotherapy for:

• Brain metastases
• Cancer treatment

Approved in Switzerland as WBRT for:

• Brain metastases
• Cancer treatment

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

A study of 3459 cancer patients receiving Whole Brain Radiotherapy (WBRT) revealed that older age, male gender, and a shorter time from primary cancer diagnosis to WBRT are associated with worse overall survival outcomes.

Seventeen percent of patients died within 6 weeks of starting WBRT, indicating significant challenges in patient selection and the need for careful consideration of treatment timing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor outcomes after whole brain radiotherapy in patients with brain metastases: results from an international multicentre cohort study. Windsor, AA., Koh, ES., Allen, S., et al.[2013]

In a study of 33 patients with solitary brain metastasis, adding a 10 Gy radiation boost to the standard 40 Gy whole brain radiation therapy (WBRT) significantly improved local control and survival rates compared to WBRT alone.

Patients receiving the radiation boost had a median time to progression of 12 months and a lower cancer-related death rate (56%) compared to those who only received WBRT, who had a median time to progression of 7 months and a 100% death rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of solitary brain metastasis. Resection followed by whole brain radiation therapy (WBRT) and a radiation boost to the metastatic site. Rades, D., Raabe, A., Bajrovic, A., et al.[2022]

In a study of 275 patients with brain metastases, poor performance status and the number of metastatic sites were identified as significant predictors of early death, helping to inform treatment decisions regarding whole-brain radiotherapy (WBRT).

The regression model developed showed a high negative predictive value of 86%, indicating it can effectively identify patients unlikely to benefit from WBRT, but it had a low positive predictive value of only 45%, suggesting that further research is needed to refine patient selection for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic factors in brain metastases: can we determine patients who do not benefit from whole-brain radiotherapy? Lock, M., Chow, E., Pond, GR., et al.[2019]

A meta-analysis of 8 randomized controlled trials involving 2317 patients found that whole brain radiotherapy (WBRT) combined with radiosensitizers did not significantly improve overall survival compared to WBRT alone.

There was also no notable difference in local brain tumor response or progression between the two treatment approaches, indicating that the addition of radiosensitizers may not enhance the effectiveness of WBRT for brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole brain radiotherapy with radiosensitizer for brain metastases. Viani, GA., Manta, GB., Fonseca, EC., et al.[2021]

Stereotactic radiosurgery alone effectively controlled brain metastases in 172 patients, achieving a local tumor control rate of 87% and a median survival time of 8 months, with better outcomes for younger patients and those with stable primary tumors.

The study suggests that whole brain radiotherapy (WBRT) may not be necessary as an initial treatment for selected patients, particularly those with one or two tumors and favorable prognostic factors, as it could lead to unnecessary neurological toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? Hasegawa, T., Kondziolka, D., Flickinger, JC., et al.[2022]

A study of 100 patients receiving whole-brain radiation therapy (WBRT) found that clinically significant xerostomia (dry mouth) developed in many patients, with scores increasing from a baseline of 7 to 21 points immediately after treatment, indicating a substantial adverse effect.

The severity of xerostomia was closely linked to the radiation dose received by the parotid glands, suggesting that delineating these glands during treatment could help minimize this toxic effect, which is particularly important for patients with limited survival expectations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose. Wang, K., Pearlstein, KA., Moon, DH., et al.[2022]

Whole brain radiation therapy (WBRT) is effective in treating multiple brain metastases in lung cancer patients, improving neurological symptoms, quality of life, and prolonging survival, despite potential late complications affecting neurocognitive function.

For patients with good performance status and 3 or fewer brain metastases, focal therapy (surgery or radiosurgery) can be a viable alternative to WBRT, avoiding its associated toxicities without compromising survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of brain metastases in lung cancer: strategies to avoid/reduce late complications of whole brain radiation therapy. Shaw, MG., Ball, DL.[2021]

Patients with non-small cell lung cancer who received whole-brain radiation therapy (WBRT) in addition to stereotactic radiosurgery (SRS) had a significantly higher incidence of delayed white matter leukoencephalopathy compared to those who only received SRS, with 97.3% of WBRT patients developing this condition.

The study found that 70.8% of WBRT patients experienced severe leukoencephalopathy (grade 3), while only 1 patient in the SRS-only group developed any leukoencephalopathy, highlighting the increased risk associated with WBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer. Monaco, EA., Faraji, AH., Berkowitz, O., et al.[2022]

In a study of 33 patients with single brain metastases treated with involved field radiation therapy (IFRT) after surgery, local control rates were high, with 90.3% at 12 months and 85.8% at 24 months, indicating effective management of the surgical site.

IFRT provided a promising alternative to whole brain radiation therapy (WBRT), as it reduced the risk of delayed neurotoxicity while maintaining reasonable overall survival rates of 65.6% at 12 months and 61.5% at 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involved field radiation therapy after surgical resection of solitary brain metastases--mature results. Connolly, EP., Mathew, M., Tam, M., et al.[2021]

In a study of 134 patients with 1-3 brain metastases, those receiving intensified treatments (surgery plus WBRT or SRT-WBRT) showed better local response and control compared to those receiving WBRT alone, highlighting the efficacy of combined treatment approaches.

While about 60% of patients experienced mild acute toxicity, severe side effects were rare, suggesting that intensified treatments are relatively safe and can improve survival outcomes without significantly increasing the risk of severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis. Buglione, M., Pedretti, S., Gipponi, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Poor outcomes after whole brain radiotherapy in patients with brain metastases: results from an international multicentre cohort study. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Treatment of solitary brain metastasis. Resection followed by whole brain radiation therapy (WBRT) and a radiation boost to the metastatic site. [2022]

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

Prognostic factors in brain metastases: can we determine patients who do not benefit from whole-brain radiotherapy? [2019]

4. England pubmed.ncbi.nlm.nih.gov

Whole brain radiotherapy with radiosensitizer for brain metastases. [2021]

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

Brain metastases treated with radiosurgery alone: an alternative to whole brain radiotherapy? [2022]

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

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose. [2022]

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

Treatment of brain metastases in lung cancer: strategies to avoid/reduce late complications of whole brain radiation therapy. [2021]

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

Leukoencephalopathy after whole-brain radiation therapy plus radiosurgery versus radiosurgery alone for metastatic lung cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Involved field radiation therapy after surgical resection of solitary brain metastases--mature results. [2021]

10. Italy pubmed.ncbi.nlm.nih.gov

The treatment of patients with 1-3 brain metastases: is there a place for whole brain radiotherapy alone, yet? A retrospective analysis. [2022]