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

Trial Summary

What is the purpose of this trial?

To learn if consolidative stereotactic radiosurgery (cSRS) can help to control central nervous system (CNS) disease in patients who have brain metastases and have a partial response or stable brain metastases after systemic therapy. To learn if using SRS to treat all brain metastases that do not respond to systemic therapy versus treating only metastases that are getting worse can help to control CNS disease in patients whose disease gets worse after systemic therapy.

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.

What data supports the effectiveness of the treatment Stereotactic Radiosurgery for brain cancer?

Research shows that Stereotactic Radiosurgery (SRS) is effective for treating brain metastases, improving outcomes and reducing side effects compared to whole-brain radiation therapy. It is particularly beneficial for patients with controlled systemic disease and can be used to treat multiple brain tumors in a single session. ^{1 2 3 4 5}

Is stereotactic radiosurgery safe for humans?

Research shows that stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) are generally safe for humans, with a focus on minimizing side effects like neurotoxicity (damage to the nervous system). These treatments have been used safely in conditions like brain metastases and lung cancer, with ongoing emphasis on quality and patient safety. ^{6 7 8 9 10}

How is the treatment of systemic therapy combined with stereotactic radiosurgery unique for brain cancer?

This treatment is unique because it combines systemic therapy (which treats the whole body) with stereotactic radiosurgery (a precise form of radiation therapy) to target brain cancer, potentially offering a more focused approach than traditional whole brain radiation therapy. Stereotactic radiosurgery, like CyberKnife, allows for precise targeting of brain tumors, which may reduce damage to surrounding healthy tissue. ^{2 11 12 13 14}

Research Team

Thomas H Beckham, MD,PHD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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) 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]

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 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]

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]

References

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

Patients with Long-Term Control of Systemic Disease Are a Favorable Prognostic Group for Treatment of Brain Metastases with Stereotactic Radiosurgery Alone. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Intracranial control after Cyberknife radiosurgery to the resection bed for large brain metastases. [2018]

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

Stereotactic radiosurgery and fractionated stereotactic radiosurgery for vestibular schwannomas: A comparison of clinical outcomes from the RSSearch patient registry. [2022]

4. Scotland pubmed.ncbi.nlm.nih.gov

Pattern of disease progression following stereotactic radiosurgery in malignant glioma patients. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Guidelines for Multiple Brain Metastases Radiosurgery. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

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

Efficacy and safety of CyberKnife radiosurgery in elderly patients with brain metastases: a retrospective clinical evaluation. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer. [2022]

10. 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]

11. Poland pubmed.ncbi.nlm.nih.gov

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review. [2022]

12. Turkey pubmed.ncbi.nlm.nih.gov

Stereotactic Radiosurgery Results in Non-Small-Cell Lung Cancer Patients with Brain Metastases in the Era of Modern Systemic Treatment Agents. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Cumulative Doses to Brain and Other Critical Structures After Multisession Gamma Knife Stereotactic Radiosurgery for Treatment of Multiple Metastatic Tumors. [2022]

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

Linear accelerator radiosurgery in the treatment of brain metastases. [2022]