Brain Tumor > Hippocampal-avoidant (HA-WBRT) Radiotherapy

Stereotactic Radiosurgery vs. HA-WBRT + Memantine for Brain Cancer

Recruiting in Palo Alto (17 mi)

+78 other locations

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Canadian Cancer Trials Group

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Stereotactic radiosurgery (SRS) is a commonly used treatment for brain tumors. It is a one-day (or in some cases two day), out-patient procedure during which a high dose of radiation is delivered to small spots in the brain while excluding the surrounding normal brain. Whole brain radiation therapy with hippocampal avoidance (HA-WBRT) is when radiation therapy is given to the whole brain, while trying to decrease the amount of radiation that is delivered to the area of the hippocampus. The hippocampus is a brain structure that is important for memory. Memantine is a drug that is given to help relieve symptoms that can be caused by WBRT, including problems with memory and other mental symptoms. Health Canada, the regulatory body that oversees the use of drugs in Canada, has not approved the sale or use of memantine in combination with WBRT to treat this kind of cancer, although they have allowed its use in this study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using NMDA antagonists like amantadine, ketamine, or dextromethorphan.

How is the treatment of Stereotactic Radiosurgery vs. HA-WBRT + Memantine for brain cancer different from other treatments?

This treatment is unique because it combines Stereotactic Radiosurgery (SRS), which precisely targets brain tumors, with Hippocampal-avoidant Whole Brain Radiation Therapy (HA-WBRT) that spares the hippocampus to reduce memory and cognitive side effects, and memantine, a drug that may help protect brain function.

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Is Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) safe for humans?

Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) is designed to reduce cognitive decline compared to standard whole brain radiotherapy, and studies suggest it is generally safe, with a focus on preserving brain function while treating brain metastases.

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

Research indicates that hippocampal avoidance whole brain radiotherapy (HA-WBRT) can help preserve neurocognitive function compared to conventional whole brain radiotherapy, making it a promising treatment for patients with brain metastases.

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Eligibility Criteria

This trial is for adults with 5 to 15 brain metastases from non-blood cancers, where the largest tumor is smaller than 2.5 cm. They must be able to undergo specific types of radiosurgery and HA-WBRT at certified centers, complete neurocognitive tests, and use effective contraception if needed. Excluded are pregnant/nursing individuals, those with allergies to gadolinium or memantine, prior cranial radiation therapy recipients, patients with certain brain conditions or liver disease.

Inclusion Criteria

My cancer is not related to blood and has been confirmed by a lab test.

My largest brain tumor is smaller than 2.5 cm.

I can take care of myself and am up and about more than half of my waking hours.

I am older than 18 years.

I have between 5 and 15 brain tumors as shown on a recent MRI.

Exclusion Criteria

I have had radiation therapy to my brain before.

I cannot undergo a brain MRI.

I am scheduled for chemotherapy around the time of my radiation treatment.

My cancer has spread to the lining of my brain and spinal cord.

My brain cancer is near my optic nerve or chiasm.

I have over 15 brain tumors as shown in my recent MRI.

I am currently taking NMDA antagonist medication.

I have been diagnosed with chronic liver disease or cirrhosis.

I am of childbearing age and do not plan to use birth control.

I have had surgery to remove a brain tumor that spread from another part of my body.

My cancer is a type of germ cell tumor, small cell carcinoma, or lymphoma.

Participant Groups

The study compares Stereotactic Radiosurgery (SRS), a precise one-day radiation treatment targeting tumors while sparing normal brain tissue, against Whole Brain Radiotherapy avoiding the hippocampus (HA-WBRT) plus Memantine which aims to protect memory during whole-brain treatment. The effectiveness in controlling cancer spread within the brain and impact on memory will be assessed.

Group I: Stereotactic Radiosurgery (SRS) Experimental Treatment 1 Intervention

SRS 18-20 or 22Gy in single fraction

Group II: Hippocampal-avoidant (HA-WBRT) plus Memantine Experimental Treatment 2 Interventions

WBRT 30Gy in 10 fractions + memantine

Hippocampal-avoidant (HA-WBRT) Radiotherapy is already approved in United States, Canada, European Union for the following indications:

🇺🇸 Approved in United States as HA-WBRT for:

• Brain metastases

🇨🇦 Approved in Canada as HA-WBRT for:

• Research use only, not approved for general use

🇪🇺 Approved in European Union as HA-WBRT for:

• Brain metastases

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Mission Hospital Asheville, NC

Siteman Cancer Center at Saint Peters Hospital Saint Peters, MO

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon, NH

Loyola University Medical Center Maywood, IL

More Trial Locations

Who is running the clinical trial?

Canadian Cancer Trials Group Lead Sponsor

Alliance for Clinical Trials in Oncology Collaborator

NRG Oncology Collaborator

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] Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique.

2. 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] Whole brain radiotherapy (WBRT) is a vital tool in radiation oncology and beyond, but it can result in adverse health effects such as neurocognitive decline. Hippocampal Avoidance WBRT (HA-WBRT) is a strategy that aims to mitigate the neuro-cognitive side effects of whole brain radiotherapy treatment by sparing the hippocampi while delivering the prescribed dose to the rest of the brain. Several competing modalities capable of delivering HA-WBRT, include: Philips Pinnacle step-and-shoot intensity modulated radiotherapy (IMRT), Varian RapidArc volumetric modulated arc therapy (RapidArc), and helical TomoTherapy (TomoTherapy).

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

Radiological distribution of brain metastases and its implication for the hippocampus avoidance in whole brain radiotherapy approach. [2018] Hippocampus avoidance in whole brain radiotherapy (HA-WBRT) offers the feasibility of less-impaired cognitive function than conventional WBRT. The study aims to assess the radiological distribution of brain metastases (BMs) with relation to the hippocampus and peri-hippocampus region as defined by the RTOG 0933 for better understanding of margin definition in HA-WBRT treatment planning.

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

Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial. [2021] Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function.

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

Dosimetric feasibility of hippocampal avoidance whole brain radiotherapy with an MRI-guided linear accelerator. [2022] Whole brain radiotherapy with hippocampal avoidance (HA-WBRT) is a technique utilized to treat metastatic brain disease while preserving memory and neurocognitive function. We hypothesized that the treatment planning and delivery of HA-WBRT plans is feasible with an MRI-guided linear accelerator (linac) and compared plan results with clinical non-MRI-guided C-Arm linac plans.

6. 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] Whole-brain radiotherapy is associated with neurocognitive decline and decreased quality-of-life (QOL) among survivors of brain metastasis. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) has shown advantage in delaying or preventing the neurocognitive decline while maintaining disease control. This study was done to assess the benefits and feasibility of HA-WBRT in patients with cerebral metastasis in terms of preservation of neurocognitive function and quality of life.

7. England pubmed.ncbi.nlm.nih.gov

Evaluating the Heterogeneity of Hippocampal Avoidant Whole Brain Radiotherapy Treatment Effect: A Secondary Analysis of NRG CC001. [2023] Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases (BM). This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.