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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation treatment for brain cancer that has spread from other parts of the body. It employs WBRT-PRDR (Whole Brain Radiation Therapy with Pulsed Reduced Dose Rate), which distributes the radiation dose to potentially minimize side effects. Participants will also take memantine, a drug that may help protect brain function during treatment. The trial seeks individuals with brain cancer originating elsewhere in the body, who have undergone previous treatment for brain metastases, and can manage daily activities well. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important research.

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.

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

Research has shown that whole-brain radiation therapy (WBRT) is generally safe, though it can cause side effects. Early side effects are usually mild, such as temporary hair loss and fatigue. However, later on, some individuals might experience memory problems or difficulty concentrating.

The pulsed reduced dose rate (PRDR) technique may help reduce some common side effects of repeated radiation treatments, according to research involving many patients. This suggests that patients might experience fewer severe side effects compared to standard methods.

Memantine, a medication used in this treatment, is FDA-approved to assist with memory and learning issues. Its use in other situations has demonstrated safety, indicating it is well-tolerated.

Overall, while WBRT-PRDR plus memantine appears promising, awareness of potential early and late side effects is important. Researchers closely monitor participants in clinical trials like this to manage any adverse events. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the PRDR WBRT treatment for brain cancer because it offers a new twist on traditional whole-brain radiation therapy (WBRT). Unlike standard WBRT, this approach uses a Pulsed Reduced Dose Rate (PRDR) technique, which delivers radiation in a way that may reduce damage to healthy brain tissue. This could potentially lead to fewer cognitive side effects, which is a significant improvement over existing options. Moreover, the addition of memantine, a drug typically used to treat symptoms of Alzheimer's, could help further protect brain function during treatment.

What evidence suggests that WBRT-PRDR plus memantine could be effective for brain cancer?

Research has shown that whole-brain radiation therapy (WBRT) effectively treats cancer cells that have spread to the brain. In this trial, participants will receive a newer method called pulsed reduced dose rate (PRDR) WBRT, which delivers radiation more slowly and may reduce side effects. Studies have found that this slower method still effectively targets cancer cells. Additionally, participants will receive memantine, a drug that can help with memory and may protect brain function during treatment. Together, these treatments aim to improve outcomes for patients with brain cancer. ^{2 5 6 7 8}

Who Is on the Research Team?

Lindsay Puckett, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10295923/

PRO: Do We Still Need Whole-Brain Irradiation for Brain ... The available data suggest that modern WBRT techniques can play a significant role in the treatment of multiple brain metastases and warrant ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1879850021001090

Critical Review Radiation Therapy for Brain Metastases Treatment options for brain metastases include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), surgery, and systemic therapies.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483798/

Whole brain radiation therapy (WBRT) alone versus WBRT ... This article is an update of "Whole brain radiation therapy (WBRT) alone versus WBRT and radiosurgery for the treatment of brain metastases"

4. advancesradonc.org advancesradonc.org/article/S2452-1094(20)30170-6/pdf

Outcomes From Whole-Brain Reirradiation Using Pulsed ... Here, we report our experience using whole-brain pulsed reduced dose rate radiation therapy (PRDR), a method that delivers radiation at a slower rate of 0.067 ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/38/12/6835

Whole-Brain Radiotherapy (WBRT) for Brain Metastases This retrospective study investigated the impact of the interval between diagnosis of brain metastases and WBRT plus ten additional factors on overall survival ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7557211/

Outcomes From Whole-Brain Reirradiation Using Pulsed ... In this large cohort of patients with advanced intracranial metastases, PRDR achieves acceptable survival and may decrease toxicity associated with ReRT.

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/results/NCT03746080

Study Results | NCT03746080 | Whole Brain Radiation ... After completion maximal safe surgical resection, patients undergo radiation therapy for 42 days, initiating whole brain radiation therapy at day 21 (dose 16 of ...

8. withpower.com withpower.com/trial/phase-3-brain-neoplasms-10-2021-c13cf

PRDR WBRT for Brain Cancer 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 ...