Radiation Therapy for Brain Metastasis

Recruiting at 242 trial locations

Overseen By Luke R. Pike

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Disqualifiers: Leptomeningeal disease, Brainstem metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1-2 weeks

269 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether fractionated stereotactic radiosurgery (FSRS) is more effective than the standard method for treating cancer that has spread to the brain. FSRS divides the radiation treatment into three sessions, while the standard method delivers it in one session. The trial aims to determine which approach better shrinks tumors. It may suit individuals with certain cancers, such as lung or breast cancer, who have 1 to 8 brain tumors not located in the brainstem. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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.

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

Research shows that both treatments in this trial, Stereotactic Radiosurgery (SRS) and Fractionated Stereotactic Radiation Therapy (FSRS), are generally well-tolerated.

SRS precisely targets brain tumors with radiation and effectively controls tumor growth in the treated area. A review of many studies involving 1,446 patients found that SRS was effective and safe for treating brain metastases.

Similarly, FSRS, which involves administering radiation over several sessions, also appears safe. Research suggests that FSRS effectively controls tumor growth while minimizing severe side effects. Patients receiving this treatment have shown low rates of serious neurological issues, making it a promising option for treating brain metastases.

Extensive studies indicate that both treatments are safe options for patients with cancer that has spread to the brain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these radiation therapies for brain metastasis because they offer more precise targeting of tumors. Fractionated Stereotactic Radiation Therapy (FSRS) delivers radiation in smaller doses over multiple sessions, potentially reducing damage to healthy brain tissue compared to traditional whole-brain radiation. Stereotactic Radiosurgery (SRS) provides a single-session, high-dose treatment, which can be more convenient and quicker than other methods. These advanced techniques aim to improve patient outcomes by minimizing side effects while effectively targeting cancer cells.

What evidence suggests that this trial's treatments could be effective for brain metastasis?

This trial will compare two treatments for brain metastases: stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (FSRS). Research has shown that both FSRS and SRS effectively treat brain metastases. Participants may receive SRS, which precisely targets tumors and consistently controls them, whether there is one or several. Alternatively, participants may receive FSRS, which delivers radiation over multiple sessions and has demonstrated a high rate of local tumor control with few severe side effects. Some studies suggest FSRS effectively controls tumors, making it a promising choice. Both treatments use high-energy x-rays to kill tumor cells, but FSRS might have an advantage by spreading out the treatment, potentially reducing side effects. ^{1 4 6 7 8}

Who Is on the Research Team?

Rupesh R Kotecha, MD

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

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 can care for myself but may need occasional help.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Fractionated Stereotactic Radiation Therapy
• Stereotactic Radiosurgery

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Approved in European Union as Fractionated Stereotactic Radiotherapy for:

• Brain metastases

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5707424/

Fractionated stereotactic radiation therapy for intact brain ... FSRT for brain metastases appears to demonstrate a high rate of local control with minimal risk of severe toxicity.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4630352/

Efficacy and Safety of Fractionated Stereotactic Radiosurgery ... The median OS was 16 months, and the estimated OS rates at 6, 12 and 18 months were 81.1%, 56.8%, and 40.7%, respectively. Of 21 patients who died, 10 (47.6%) ...

3. ar.iiarjournals.org ar.iiarjournals.org/content/43/6/2757

Treatment Outcomes After Higher-dose Fractionated ... Higher-dose FSRT appears feasible and effective in patients with 1-4 brain metastases. BED 63-66.7 Gy 12 may not improve LC and OS but may increase RN risk.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03726359

Phase I Study of Fractionated Stereotactic Radiation ... The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02277-6

Fractionated stereotactic radiotherapy of brain metastases FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases.

6. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001708

Fractionated stereotactic radiotherapy of brainstem ... FSRT for BSM is as an effective and safe treatment approach with high LC rates and reasonable neurological toxicity despite the poor prognosis.

7. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2835449

Preop vs Postop Stereotactic Radiation Therapy: Trial Analysis Overall, these trials demonstrated that postoperative SRS is associated with high rates of local control with minimum adverse effects, while ...

8. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1471004/full

Analysis of linear accelerator-based fractionated ... Results: Results as of December 2023 showed median intracranial progression-free survival (iPFS) at 12.4 months, with median overall survival (OS) not reached ...