What is the mechanism of action of this treatment?

Stereotactic radiosurgery (SRS) is a common treatment for brain metastasis that uses high-dose, targeted radiation to kill tumor cells while minimizing damage to surrounding healthy tissue. This precision is particularly important for brain metastasis patients as it helps preserve cognitive function and reduces other side effects. Whole brain radiation therapy (WBRT) delivers lower doses of radiation to the entire brain over several treatments, which can control widespread metastatic disease but has a higher risk of neurocognitive side effects. Understanding these mechanisms aids in selecting the most appropriate treatment based on the extent of metastasis and the patient's overall health.

What side effects are associated with this type of intervention?

Stereotactic radiosurgery (SRS) for brain metastasis is associated with side effects such as radiation necrosis, which can lead to cerebral edema and focal neurologic symptoms. Whole-brain radiation therapy (WBRT) can result in neurocognitive decline and leukoencephalopathy. Both treatments aim to control brain metastases but carry specific risks that should be considered when choosing the appropriate therapy.

What prior FDA approvals exist?

The FDA has approved several treatments for brain metastasis, including stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT). SRS, a high-dose, targeted radiation therapy, is designed to kill tumor cells while minimizing damage to surrounding healthy tissue. This method has been particularly effective in treating limited brain metastases and is often preferred due to its precision and reduced cognitive side effects compared to WBRT. Other related drugs and therapies, such as temozolomide and erlotinib, have been studied in combination with radiation therapies, although their benefits over radiation alone remain under investigation.

What other types of research exist?

Promising novel alternatives to Stereotactic Radiosurgery for brain metastasis patients include: 1) Cesium-131 brachytherapy, which provides durable salvage treatment for recurrent brain metastases; 2) Magnetic resonance-guided laser ablation, which improves local control for post-radiosurgery recurrence and/or radiation necrosis; 3) ONC201, an investigational oral compound showing potential in H3 K27M-mutant gliomas; and 4) DNX-2401, an oncolytic adenovirus administered by catheter infusion, currently under study for its efficacy in brain tumors.

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Radiation Therapy

Radiosurgery vs Whole Brain Radiation for Brain Metastasis

Phase 3

Waitlist Available

Led By Jing Li

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

All patients must have histological proof of malignant cancer, which is metastatic. Histological proof may be obtained from the primary tumor or another metastatic site. However, cytology alone is not an acceptable method of diagnosis

All patients must be >/= 18 years of age

Must not have

Patients will be excluded if they have had prior surgical resection of metastatic cancer from the brain

Patients will be excluded if there is radiographic or CSF cytological evidence of leptomenengial disease

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial compares two radiation treatments for brain tumors from non-melanoma cancers. One treatment is a focused, high-dose method, while the other treats the entire brain over several sessions. The goal is to determine which method controls tumors better and has fewer side effects on thinking and memory. The focused, high-dose method has been increasingly used over the past years as an effective treatment for brain metastases, often replacing the whole brain treatment due to its ability to improve outcomes and reduce side effects.

Who is the study for?

This trial is for adults with non-melanoma cancer that has spread to the brain, with 3-15 detectable lesions on MRI. Participants must have proof of malignant cancer and be able to undergo all treatments proposed. They should not have had prior brain surgery or whole-brain radiation, no melanoma or certain other cancers, and women of childbearing age must not be pregnant.

What is being tested?

The study compares stereotactic radiosurgery (SRS), which targets tumors directly in a single high dose, against whole-brain radiotherapy (WBRT) that treats the entire brain over multiple sessions. The goal is to determine which method is more effective for treating brain metastases from non-melanoma cancers and causes fewer cognitive side effects.

What are the potential side effects?

Potential side effects include damage to normal tissue surrounding the tumor, cognitive and memory problems especially associated with WBRT, fatigue, headaches, hair loss from radiation exposure, skin irritation at treatment sites, and possible short-term swelling within the brain.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is confirmed to be spreading, based on a tissue sample.

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I am 18 years old or older.

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All my cancer spots can be treated with focused radiation because they are small enough.

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My liver, kidney, and blood tests are within normal ranges.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have not had surgery to remove cancer from my brain.

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I do not have cancer spread to the lining of my brain and spinal cord.

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I do not have melanoma, small cell carcinoma, lymphoma/leukemia, or germ cell cancer.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Local control rate

Proportion of patients with neurocognitive decline

Secondary study objectives

Cumulative incidence of local failure

Cumulative incidence of neurocognitive decline

Time to local failure

+1 more

Side effects data

From 2019 Phase 2 trial • 32 Patients • NCT01573702

32%

Fatigue

28%

Lymphocyte count decreased

24%

Cough

20%

Back pain

20%

Rash acneiform

16%

Anorexia

16%

Dry skin

16%

Hyperglycemia

16%

Rash maculo-papular

12%

Aspartate aminotransferase increased

12%

Non-cardiac chest pain

12%

Diarrhea

12%

Dyspepsia

12%

Headache

12%

Nausea

12%

Pain

12%

Pain in extremity

Urinary tract pain

Weight loss

Watering eyes

Myalgia

Wheezing

Arthralgia

Edema limbs

Abdominal pain

Paronychia

Pruritus

Blurred vision

Skin and subcutaneous tissue disorders - Other, specify

Upper respiratory infection

Vomiting

Urinary tract infection

White blood cell decreased

Lethargy

Sore throat

Skin infection

Urinary urgency

Insomnia

Infusion site extravasation

Ear pain

Oral hemorrhage

Conjunctivitis

Alkaline phosphatase increased

Blood bilirubin increased

Bone pain

Bruising

Depression

Dry eye

Dysgeusia

Dysphagia

Edema face

Epistaxis

Flashing lights

Flu like symptoms

Gastroesophageal reflux disease

Hot flashes

Hyperkalemia

Hypernatremia

Nail loss

Nail ridging

Neck pain

Neutrophil count decreased

Papulopustular rash

Platelet count decreased

Pneumonitis

Fracture

Fall

Skin hyperpigmentation

100%

80%

60%

40%

20%

Study treatment Arm

Stereotactic Radiosurgery Followed by Erlotinib

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (WBRT)Experimental Treatment3 Interventions

Patients undergo WBRT 5 days per week (7 days per week for inpatients) for 2 weeks.

Group II: Arm I (SRS)Experimental Treatment3 Interventions

Patients undergo SRS on day 1.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Whole-Brain Radiotherapy

2012

Completed Phase 2

~150

Stereotactic Radiosurgery

2021

Completed Phase 2

~440

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Stereotactic radiosurgery (SRS) is a common treatment for brain metastasis that uses high-dose, targeted radiation to kill tumor cells while minimizing damage to surrounding healthy tissue. This precision is particularly important for brain metastasis patients as it helps preserve cognitive function and reduces other side effects. Whole brain radiation therapy (WBRT) delivers lower doses of radiation to the entire brain over several treatments, which can control widespread metastatic disease but has a higher risk of neurocognitive side effects. Understanding these mechanisms aids in selecting the most appropriate treatment based on the extent of metastasis and the patient's overall health.