Radiation Therapy for Brain Metastasis

Recruiting at 135 trial locations

Overseen By Rupesh Kotecha

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NRG Oncology

Disqualifiers: Leptomeningeal disease, Brainstem metastases, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effectiveness of fractionated stereotactic radiosurgery (FSRS) to usual care stereotactic radiosurgery (SRS) in treating patients with cancer that has spread from where it first started to the brain. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. FSRS delivers a high dose of radiation to the tumor over 3 treatments. SRS is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. FSRS may be more effective compared to SRS in treating patients with cancer that has spread to the brain.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Fractionated Stereotactic Radiation Therapy for brain metastasis?

Research shows that Fractionated Stereotactic Radiotherapy (FSRT) is effective for treating brain metastases, especially for larger lesions, due to its superior control and lower toxicity rates compared to other methods. It combines precise targeting with the benefits of spreading out the radiation dose over multiple sessions, which can help protect healthy tissue. ^{1 2 3 4 5}

Is radiation therapy for brain metastasis generally safe for humans?

Radiation therapy techniques like Stereotactic Radiosurgery (SRS) and Stereotactic Body Radiation Therapy (SBRT) are widely used and considered safe, but they can have serious complications. Safety measures and quality assurance are important to minimize risks, and ongoing research focuses on improving these aspects. ^{2 4 6 7 8}

How is the treatment for brain metastasis using fractionated stereotactic radiation therapy different from other treatments?

Fractionated stereotactic radiation therapy (FSRT) is unique because it delivers precise radiation in multiple smaller doses, which can be more effective and less toxic for larger brain metastases compared to single-dose treatments like stereotactic radiosurgery (SRS). This approach allows for better control of tumor growth while minimizing damage to surrounding healthy tissue. ^{2 4 5 7 9}

Research Team

Rupesh R Kotecha, MD

Principal Investigator

NRG Oncology

Eligibility Criteria

This trial is for patients with certain cancers (like melanoma, lung, breast, kidney cancer) that have spread to the brain. Participants must be eligible for high-energy x-ray treatments and should not have conditions that exclude them from radiation therapy.

Inclusion Criteria

I do not have any infections needing IV antibiotics.

I am planning to have surgery for up to 2 cancer lesions.

I am 18 years old or older.

Exclusion Criteria

I do not have a recent severe lung problem that would stop me from receiving the study treatment.

I have liver problems causing jaundice or blood clotting issues.

NYHA Functional Classification III/IV

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either SRS for 1 fraction or FSRS for 3 fractions, along with CT and MRI on study

1-2 weeks

1-3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 1 year, every 4 months for 1 year, then every 6 months for 3 years

Treatment Details

Interventions

• Fractionated Stereotactic Radiation Therapy (Radiation)
• Stereotactic Radiosurgery (Radiation)

Trial Overview The study compares two types of radiation therapy: Fractionated Stereotactic Radiation Therapy (FSRS), given over three sessions, versus a single-session Stereotactic Radiosurgery (SRS). The goal is to see if FSRS is more effective in treating brain tumors from cancer spread.

Participant Groups

Group I: ARM II (FSRS) Experimental Treatment 3 Interventions

Patients undergo FSRS over 30-90 minutes for 3 fractions on study. Additionally, patients undergo CT and MRI on study.

Group II: ARM I (SRS) Active Control 3 Interventions

Patients undergo SRS over 30-90 minutes for 1 fraction on study. Additionally, patients undergo CT and MRI on study.

Fractionated Stereotactic Radiation Therapy is already approved in Canada, Japan for the following indications:

Approved in Canada as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Approved in Japan as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Who Is Running the Clinical Trial?

NRG Oncology

Lead Sponsor

Trials

242

Recruited

105,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Fractionated stereotactic radiotherapy (FSRT) is a safe and effective treatment for cavernous sinus meningiomas, achieving a local progression-free survival rate of 93% over a median follow-up of 50 months among 30 patients.

The treatment led to improvement in preexisting neurological symptoms for 50% of patients, with only a small number experiencing late radiation toxicity, indicating good tolerance and minimal cognitive decline post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus meningioma: functional outcome, local control, and tolerance. Brell, M., Villà, S., Teixidor, P., et al.[2018]

Stereotactic radiotherapy, including SRS, FSRT, and SBRT, is recognized as a guideline-recommended treatment for both malignant and benign tumors, as well as for certain neurological and vascular disorders.

The German Society for Radiation Oncology and the German Society for Medical Physics have established consensus statements outlining the necessary definitions and quality standards for stereotactic radiotherapy to ensure optimal clinical outcomes and treatment quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Definition and quality requirements for stereotactic radiotherapy: consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery. Guckenberger, M., Baus, WW., Blanck, O., et al.[2020]

The study analyzed 24 treatment plans for 23 patients using fractionated stereotactic radiotherapy (FSRT) and found that the treatment plans achieved clinically acceptable quality indices, indicating effective management of brain metastases.

Key metrics such as the Radiation Therapy Oncology Group conformity index (mean 0.942) and the Paddick conformity index (mean 0.824) demonstrated that FSRT can be effectively tailored for various tumor volumes, ensuring safety and efficacy in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plan Quality Assessment of Fractionated Stereotactic Radiotherapy Treatment Plans in Patients With Brain Metastases. Simon, M., Papp, J., Csiki, E., et al.[2022]

Fractionated stereotactic radiotherapy (FSRT) is a safe and effective treatment for brain metastases of any size, showing excellent local control with a 12-month local failure rate of 17.8% overall.

In a study of 60 patients treated with FSRT, the median survival was 20.5 months, and the risk of radionecrosis was relatively low at 7.1%, indicating favorable toxicity outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Hypofractionated Stereotactic Radiotherapy for Small and Moderate-Sized Brain Metastases: A Single-Institution Analysis. Yan, M., Zalay, O., Kennedy, T., et al.[2022]

In a study of 66 patients with 114 brain metastases treated with fractionated stereotactic radiotherapy (FSRT) using gamma knife, significant volume changes were observed in 29% of the lesions, highlighting the importance of mid-treatment radiological reassessment.

The study found that small and cystic tumors were more likely to enlarge during treatment, while most lesions showed regression within 6 months, suggesting that adapting treatment plans based on these changes could improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interfractional change of tumor volume during fractionated stereotactic radiotherapy using gamma knife for brain metastases. Kawashima, M., Akabane, A., Noda, R., et al.[2022]

Stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) have advanced significantly, necessitating updated best practices for safety and quality assurance due to their complexity and precision in delivering high doses of radiation.

A team-based approach with trained specialists and a comprehensive quality assurance program is essential for the safe and effective implementation of SRS and SBRT, emphasizing that patient safety is a collective responsibility among all stakeholders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update. Das, IJ., Dawes, SL., Dominello, MM., et al.[2022]

Fractionated stereotactic radiation therapy (FSRT) showed an impressive 12-month local control rate of 86% for brain metastases, with even higher rates (95%) for tumors smaller than 3 cm, indicating its efficacy in managing these conditions.

The treatment was associated with minimal severe toxicity, with only 6% of patients experiencing grade 4 toxicity, and no irreversible severe side effects, making FSRT a safe option for patients who may not tolerate single-fraction treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiation therapy for intact brain metastases. Marcrom, SR., McDonald, AM., Thompson, JW., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

Stereotactic radiosurgery (SRS) is an effective treatment for patients with brain metastases, particularly prolonging survival for those with a single metastasis and maintaining functional independence for patients with up to three metastases.

As SRS technology becomes more widely used, careful patient selection and treatment planning are essential to maximize its benefits and integrate it safely with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in intracranial stereotactic radiotherapy for metastases. Pinkham, MB., Whitfield, GA., Brada, M.[2022]

References

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

Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus meningioma: functional outcome, local control, and tolerance. [2018]

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

Definition and quality requirements for stereotactic radiotherapy: consensus statement from the DEGRO/DGMP Working Group Stereotactic Radiotherapy and Radiosurgery. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Plan Quality Assessment of Fractionated Stereotactic Radiotherapy Treatment Plans in Patients With Brain Metastases. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Outcomes of Hypofractionated Stereotactic Radiotherapy for Small and Moderate-Sized Brain Metastases: A Single-Institution Analysis. [2022]

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

Interfractional change of tumor volume during fractionated stereotactic radiotherapy using gamma knife for brain metastases. [2022]

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

Quality and Safety Considerations in Stereotactic Radiosurgery and Stereotactic Body Radiation Therapy: An ASTRO Safety White Paper Update. [2022]

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

Fractionated stereotactic radiation therapy for intact brain metastases. [2022]

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

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

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

New developments in intracranial stereotactic radiotherapy for metastases. [2022]