Systemic Therapy + Stereotactic Radiosurgery for Brain Cancer

Overseen By Thomas H Bekham, MD,PHD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Targeted therapy

Disqualifiers: Leptomeningeal involvement, Small cell lung cancer, Lymphoma, Leukemia, 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

316 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a focused type of radiation called stereotactic radiosurgery (SRS) for treating brain cancer that has spread from other parts of the body. Researchers aim to determine if this treatment can better control cancer in the brain, particularly when the cancer hasn't fully responded or has worsened after initial treatments. The trial targets individuals with brain metastases that haven't required immediate surgery or radiation and can be treated with SRS. Participants should have at least one measurable brain metastasis that hasn't been treated with SRS before. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial information does not specify if 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 has shown that stereotactic radiosurgery (SRS) is generally safe for treating brain conditions. SRS uses focused radiation to target and destroy tumor cells while protecting nearby healthy tissue. Studies highlight its accuracy in treating brain tumors and similar conditions.

Data from past research indicate that most patients tolerate SRS well. Side effects, if they occur, are usually mild and short-lived, such as tiredness or headaches. These effects are less severe compared to traditional radiation treatments.

Additionally, evidence suggests that systems like the CyberKnife® can safely treat brain metastases with SRS. This technology provides targeted treatment, reducing the risk of damaging healthy brain areas.

Overall, SRS has a good safety record for similar conditions, with minimal adverse effects reported. It offers a promising way to treat brain metastases with precision and care. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using stereotactic radiosurgery (SRS) for brain cancer because it offers a precise and focused radiation treatment compared to traditional whole-brain radiation therapy. Unlike conventional methods that may affect healthy brain tissue, SRS targets only the tumor, minimizing damage to surrounding areas. This precision not only aims to improve effectiveness in shrinking tumors but also reduces side effects, potentially improving patients' quality of life. Additionally, SRS can be combined with systemic therapy, offering a comprehensive approach that might enhance overall treatment outcomes.

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

Research has shown that stereotactic radiosurgery (SRS) can be effective for cancer that has spread to the brain. In this trial, participants will be randomized into different treatment arms involving SRS. Studies have found that SRS, such as Gamma Knife radiosurgery, leads to good results with fewer cognitive issues compared to other treatments. Patients with one or a few small brain tumors have experienced significant benefits. Specifically, one study found a high chance of controlling tumor growth for up to 12 months. Additionally, SRS has demonstrated similar survival rates to whole-brain radiotherapy but with fewer side effects. These findings suggest that SRS might effectively manage brain metastases. ^{4 6 7 8 9}

Who Is on the Research Team?

Thomas H Beckham, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with brain metastases who have had a partial response or stable condition after systemic therapy. It's not specified who can't join, but typically those with certain medical conditions or treatments that conflict with the study may be excluded.

Inclusion Criteria

My medical team agrees my bone marrow doesn't need immediate treatment.

I don't have brain-related symptoms from cancer, or I manage them with a low dose of steroids.

I have been evaluated by a team of cancer and brain surgery specialists.

Exclusion Criteria

Any BM with a significant hemorrhagic component

I have had whole brain radiation therapy before.

I have a bone metastasis larger than 3 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Systemic Therapy

Participants receive upfront systemic therapy to assess response in brain metastases

12 weeks

Stereotactic Radiosurgery (SRS)

Participants with stable disease or partial response receive consolidative stereotactic radiosurgery (cSRS) or ongoing observation

4 weeks

Follow-up

Participants are monitored for safety, adverse events, and CNS progression-free survival

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Stereotactic Radiosurgery

Trial Overview

The study is testing if stereotactic radiosurgery (cSRS) can control central nervous system disease in patients whose brain metastases are partially responsive or stable following systemic therapy, and comparing different SRS approaches to treat progressing metastases.

How Is the Trial Designed?

Group I: cSRS PR or SD Experimental Treatment 2 Interventions

Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.

Group II: b-PDC CNS PD Experimental Treatment 2 Interventions

At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.

Group III: a-pdSR CNS PD Experimental Treatment 2 Interventions

At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.

Group IV: SST treated SD or PR patients to receive cSRS/ ongoing observation Experimental Treatment 2 Interventions

Patients with a CR will be observed with ongoing standard of care MRI. Patients with SD or PR will be randomized to receive cSRS or ongoing observation.

Group V: SST treated PD patients to pdSRS / pdSRS+cSRS Experimental Treatment 2 Interventions

At the time of CNS PD, patients will also be randomized to pdSRS versus pdSRS + cSRS.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., 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]

Stereotactic radiosurgery (SRS) using CyberKnife for large brain metastasis cavities (≥2 cm) showed a local failure rate of 24%, indicating it can effectively control local disease after surgery.

Patients with synchronous metastases had a higher risk of distant brain failure, suggesting that while SRS can delay the need for whole brain radiation therapy (WBRT), careful monitoring is needed for those with multiple metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. Vogel, J., Ojerholm, E., Hollander, A., et al.[2018]

In a study of 58 patients with malignant gliomas treated with stereotactic radiosurgery (SRS), 47.1% experienced local recurrence within the radiation field, indicating some localized effectiveness of SRS.

However, over half of the patients (52.9%) showed disease progression outside the SRS treatment area, suggesting that SRS alone does not significantly improve overall survival and highlighting the need for a multidisciplinary approach in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of disease progression following stereotactic radiosurgery in malignant glioma patients. Choi, SW., Cho, KR., Choi, JW., et al.[2020]

Stereotactic radiosurgery (SRS) has been shown to improve patient outcomes and reduce toxicity compared to whole-brain radiation therapy (WBRT) for treating multiple brain metastases, based on three decades of research.

Current practices allow for the treatment of patients with 10 or more brain metastases using SRS alone, even with cumulative tumor volumes of up to 25 cm³, reflecting a shift in clinical approach due to advancements in cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. Niranjan, A., Monaco, E., Flickinger, J., et al.[2019]

A retrospective analysis of 383 patients treated with stereotactic radiosurgery (SRS) for brain metastases showed a median survival of 9 months, indicating that SRS can be an effective treatment option.

The study found a 75% local control rate at one year, suggesting that SRS is a safe and effective method for managing brain metastases, particularly in selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linear accelerator radiosurgery in the treatment of brain metastases. Ulm, AJ., Friedman, WA., Bova, FJ., et al.[2022]

Both stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) achieved similar local control rates for vestibular schwannomas, with SRS showing 100% and fSRS showing 94.2%.

However, fSRS was associated with a significantly higher risk of toxicities (42.3% vs. 8.3% for SRS), indicating that while both treatments are effective, fSRS may pose greater safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry. Singh, R., Ansinelli, H., Jenkins, J., et al.[2022]

Stereotactic radiosurgery (SRS) using CyberKnife is a safe and effective treatment for elderly patients (≥65 years) with brain metastases, achieving high local control rates and maintaining a stable quality of life in 97.9% of patients.

In a study of 97 patients, SRS demonstrated a 79% overall survival rate at 3 months and a 99.2% local tumor progression-free rate at 6 months, indicating its efficacy compared to traditional whole brain radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. Acker, G., Hashemi, SM., Fuellhase, J., et al.[2021]

In a study of 102 patients receiving stereotactic ablative radiotherapy (SABR) for lung cancer and lung oligometastases, the three-year local control rates were 85% for primary lung cancer and 82% for metastatic lesions, which are comparable to global outcomes.

No severe toxicities (grade three) were reported, indicating that SABR is a safe treatment option, although Māori patients with primary lung cancer experienced significantly worse progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population. Geary, RL., Yasin, NABH., Lin, F., et al.[2021]

In a study of 106 patients with early-stage non-small cell lung cancer treated with CyberKnife® SBRT, the treatment demonstrated an 88% local control rate at 2 years, indicating its efficacy in managing this type of cancer.

The treatment was associated with low toxicity, with only 20% of patients experiencing mild fatigue and 17% mild dyspnea, and only 4% experiencing significant late effects, suggesting it is a safe option for medically inoperable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. Temming, S., Kocher, M., Stoelben, E., et al.[2022]

In a study of 49 patients with brain metastases treated with CyberKnife Stereotactic Radiosurgery (CKRS), the median overall survival was 15.5 months, indicating effective long-term outcomes.

CKRS demonstrated high local control rates of 98% at 3 months and 90% at 1 year, with no late complications such as radiation necrosis, highlighting its safety and efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review. de la Peña, C., Guajardo, JH., Gonzalez, MF., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9931898/

Outcomes of single brain metastasis treated with gamma ...

Gamma Knife Stereotactic radiosurgery(GKSR) achieved good outcomes in terms of OS with fewer neurocognitive disorders.

2.

advancesradonc.org

advancesradonc.org/article/S2452-1094(23)00230-0/fulltext

Stereotactic Radiosurgery in the Management of Brain ...

Stereotactic radiosurgery in the management of brain metastases: a case-based radiosurgery society practice guideline.

3.

nature.com

nature.com/articles/s41467-024-47998-8

Response of treatment-naive brain metastases to ...

Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone

4.

surgicalneurologyint.com

surgicalneurologyint.com/surgicalint-articles/stereotactic-radiosurgery-versus-whole-brain-radiotherapy-for-intracranial-metastases-a-systematic-review-and-meta-analysis/

Stereotactic radiosurgery versus whole-brain radiotherapy ...

SRS and WBRT exhibited similar recurrence rates and overall survival (OS) at 1 and 5 years, with WBRT being more effective in managing post-radiation LMD.

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0167814025046316

Staged Gamma Knife radiosurgery for large brain metastases

Staged Gamma Knife radiosurgery for large brain metastases resulted in an 83 % probability of local control at 12 months. •. Local control was further increased ...

6.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK542166/

Stereotactic Radiosurgery (SRS) and Stereotactic Body ... - NCBI

Radiation therapy is intended to damage abnormal tissue, eg, neoplastic tumor cells, while causing minimal injury to adjacent normal tissue.

7.

mayoclinic.org

mayoclinic.org/tests-procedures/brain-stereotactic-radiosurgery/about/pac-20384679

Brain stereotactic radiosurgery

This procedure delivers precise radiation therapy to treat brain tumors and other brain conditions.

8.

investors.accuray.com

investors.accuray.com/news-releases/news-release-details/new-data-indicates-cyberknifer-system-can-provide-safe-and?mobile=1

New Data Indicates the CyberKnife® System Can Provide ...

New Data Indicates the CyberKnife® System Can Provide a Safe and Effective Treatment Option to Control Brainstem Metastases, an Extremely ...

9.

academic.oup.com

academic.oup.com/neuro-oncology/article/27/2/479/7787241

Results of the CYBER-SPACE randomized phase 2 trial

Repeated stereotactic radiosurgery (SRS) for multiple brain metastases avoids whole-brain radiotherapy (WBRT) and neurologic death. The more ...