Surgery and Radiation vs. Radiation Alone for Brain Cancer

Not currently recruiting at 241 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: NRG Oncology

Must not be taking: Cytotoxic chemotherapy, Tyrosine inhibitors

Disqualifiers: Prior cranial radiotherapy, Leptomeningeal disease, Germ cell tumor, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 1-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the best way to treat brain cancer that has spread from other parts of the body (brain metastases). It compares two treatment plans: one where patients receive radiation therapy (stereotactic radiosurgery) before brain surgery and another where they undergo brain surgery before radiation. The goal is to determine if receiving radiation first helps prevent the cancer from returning or spreading and reduces brain scarring. This trial suits patients with 1-4 brain tumors, with at least one tumor requiring removal, who can undergo both surgery and radiation. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors should not be taken within 3 days before, on the day of, or within 3 days after the completion of stereotactic radiosurgery (SRS).

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

Research has shown that stereotactic radiosurgery (SRS) safely and effectively treats brain tumors. It uses focused radiation to precisely target tumors, protecting nearby healthy brain tissue. One study found that patients generally tolerate SRS well, though there is a slightly increased risk of new tumors developing elsewhere in the brain.

In contrast, brain surgery carries certain risks. A study showed that about 29.8% of patients experienced complications after surgery, most of which were temporary. Only about 10.6% faced long-lasting issues. Another study found that hospitals performing more surgeries tend to achieve better results, indicating that experience is crucial for safety.

Both treatments are used for brain cancer care, each with its own risks and benefits. The goal is to control tumor growth while ensuring patient safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it directly compares two treatment approaches for brain cancer: combining surgery with immediate stereotactic radiosurgery versus surgery followed by radiosurgery after a delay. The excitement comes from the potential to improve patient outcomes by refining the timing and combination of these treatments. Unlike standard options that often separate surgery and radiation by a longer period, this trial explores whether a more immediate combination can enhance effectiveness and reduce cancer recurrence. By understanding the optimal timing and sequence of these interventions, researchers hope to provide more effective and personalized care for brain cancer patients.

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

This trial will compare the effectiveness of surgery combined with stereotactic radiosurgery (SRS) versus SRS alone for treating brain cancer. Research has shown that surgery plays a crucial role in treating brain tumors, helping patients live longer and feel better. New surgical methods have improved patient outcomes. Surgery often serves as the first and most common treatment for brain tumors and, in some cases, may be the only treatment needed.

Studies have found that stereotactic radiosurgery (SRS) effectively treats brain tumors that have spread. SRS uses precise, high-dose radiation to target tumors while protecting healthy brain tissue. It has successfully stopped tumor growth or even shrunk tumors over time. This trial will evaluate whether combining surgery and SRS offers a more comprehensive approach to treating brain cancer, potentially reducing symptoms and preventing tumor spread. ^{6 7 8 9 10}

Who Is on the Research Team?

Stuart H Burri

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with 1-4 brain metastases, one needing surgery. Participants must have a lesion larger than 2cm but smaller than 5cm, not near the optic chiasm or in the brainstem, and be able to tolerate surgery and radiosurgery. They should agree to use contraception and not have had certain cancers or prior cranial radiotherapy.

Inclusion Criteria

I have had cancer other than in the brain diagnosed in the last 3 years.

My brain metastases are not near the optic nerve or in the brainstem.

My surgeon believes the tumor can be completely removed safely.

Exclusion Criteria

I am scheduled for chemotherapy or specific targeted therapy soon.

I am scheduled for surgery to remove more than one brain tumor.

My cancer is either a germ cell tumor, small cell carcinoma, or lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either pre-operative or post-operative stereotactic radiosurgery and surgery

1-4 weeks

1 visit (in-person) for surgery and radiosurgery

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Every 3 months for 2 years, then every 6 months for additional 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Brain Surgery
• Stereotactic Radiosurgery

Trial Overview The study compares adding stereotactic radiosurgery (high-dose radiation targeting only cancer areas) before or after surgical removal of brain tumors. It aims to see which sequence is more effective at controlling tumor growth and reducing symptoms.

How Is the Trial Designed?

Group I: Arm II (stereotactic radiosurgery, surgery) Experimental Treatment 4 Interventions

Within 7 days before surgery, patients undergo stereotactic radiosurgery for 1 fraction. Patients undergo surgery per standard of care.

Group II: Arm I (surgery, stereotactic radiosurgery) Active Control 4 Interventions

Patients undergo surgery per standard of care. Within 10-30 days after surgery, patients undergo stereotactic radiosurgery for 1 fraction.

Brain Surgery is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Vascular malformations

Approved in United States as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Epilepsy
• Trigeminal neuralgia

Approved in Canada as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Vascular malformations

Approved in Japan as Brain Surgery for:

• Brain metastases
• Primary brain tumors
• Epilepsy

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

A new classification system for neurosurgical complications was developed and validated, categorizing adverse events into five groups based on their underlying causes, which can improve the understanding and management of these events.

During a one-year study involving 115 complications, nearly half were identified as critical events, highlighting the need for targeted interventions, especially in vascular neurosurgery, which had the highest complication rate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining a new neurosurgical complication classification: lessons learned from a monthly Morbidity and Mortality conference. Gozal, YM., Aktüre, E., Ravindra, VM., et al.[2019]

Surgical removal of solitary brain metastases in non-critical areas can be beneficial, especially when the diagnosis is uncertain, based on the treatment of 1895 patients in two studies.

For patients with multiple brain metastases or when surgery is not feasible, radiation therapy combined with steroids is effective, and short-course low-dose radiation can be as effective as longer, more aggressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of surgery and radiation therapy on patients with brain metastases. Hendrickson, FR., Lee, MS., Larson, M., et al.[2019]

Patients in Monmouth County who underwent surgical resection of single brain metastases followed by whole brain radiotherapy experienced longer survival and improved quality of life compared to those treated with radiotherapy alone.

Optimal outcomes were observed when there was no active disease at the primary site or elsewhere in the body at the time of brain metastasis diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical treatment of solitary brain metastases: Monmouth County experience. Drapkin, AJ., Kreider, CH.[2004]

Combining surgery with radiation therapy is currently the most effective treatment for central nervous system tumors, highlighting the importance of a multi-faceted approach to cancer care.

The article emphasizes the role of advanced neuroimaging techniques in enhancing the success of surgical interventions for brain tumors, suggesting that improved imaging can lead to better surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurosurgical management of brain tumors. Tatter, SB.[2012]

The review of cranial tumor surgeries revealed that complication rates can range from 9% to 40%, with deep venous thromboembolism (DVT) being the most common adverse event, occurring in 3% to 26% of cases.

Implementing standardized safety protocols, such as DVT prophylaxis and intraoperative navigation techniques, could potentially reduce the incidence of adverse events and improve patient outcomes in neurosurgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns in neurosurgical adverse events: intracranial neoplasm surgery. Wong, JM., Panchmatia, JR., Ziewacz, JE., et al.[2012]

In a study of 177 glioblastoma patients, only 7.9% developed surgical site infections (SSIs) after craniotomy, indicating that while SSIs are a concern, they are relatively infrequent in this population.

The analysis found no significant risk factors for SSIs, and surprisingly, patients who received early postoperative radiation had a lower incidence of SSIs, suggesting that rapid chemoradiation may be beneficial for optimal oncological outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical Site Infections in Glioblastoma Patients-A Retrospective Analysis. Scheer, M., Spindler, K., Strauss, C., et al.[2023]

In a study comparing 108 patients with solitary cerebral metastases, gamma knife radiosurgery alone achieved local tumor control rates comparable to surgery plus whole-brain radiation therapy (WBRT), with rates of 83% and 75% respectively.

The 1-year survival rate was slightly higher in the surgical group (53%) compared to the radiosurgery group (43%), but the difference was not statistically significant, suggesting that radiosurgery can be an effective standalone treatment for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgery and radiotherapy compared with gamma knife radiosurgery in the treatment of solitary cerebral metastases of small diameter. Muacevic, A., Kreth, FW., Horstmann, GA., et al.[2006]

Stereotactic radiosurgery (SRS) has become a significant alternative to craniotomy for treating brain metastases, particularly effective for small, multiple, and deep tumors.

SRS is often used in conjunction with whole-brain radiation therapy (WBRT) to enhance regional control of metastatic disease, improving patient outcomes in terms of survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiosurgery in the management of brain metastasis. Smith, ML., Lee, JY.[2022]

In a study of 273 craniotomies performed on pediatric patients for brain tumors, the surgical mortality rate was very low at 0.4%, indicating a high level of safety for this procedure.

Complication rates were also low, with significant issues like meningitis occurring in only 1.8% of cases and most patients (87.2%) experiencing no change or improvement in neurological function post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical mortality and selected complications in 273 consecutive craniotomies for intracranial tumors in pediatric patients. Lassen, B., Helseth, E., Egge, A., et al.[2012]

In a study of 48 patients with a single brain metastasis, those who underwent surgical resection followed by radiotherapy experienced significantly fewer recurrences of cancer in the brain (20% vs. 52%) compared to those who only received radiotherapy.

Patients who had surgery also had a longer overall survival (median 40 weeks vs. 15 weeks) and maintained functional independence for a longer period (median 38 weeks vs. 8 weeks), indicating that surgical intervention improves both survival and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of surgery in the treatment of single metastases to the brain. Patchell, RA., Tibbs, PA., Walsh, JW., et al.[2022]

In a study of 33 patients who underwent surgery for brain metastasis, 8.5% experienced peri- and postoperative adverse events (PAEs), with significant associations found between PAEs and factors like multiple brain metastases and a higher comorbidity burden.

Patients who suffered from PAEs had a much higher in-hospital mortality rate of 24% compared to just 0.6% for those without PAEs, highlighting the importance of identifying and managing risk factors to improve outcomes in vulnerable cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comorbidity Burden and Presence of Multiple Intracranial Lesions Are Associated with Adverse Events after Surgical Treatment of Patients with Brain Metastases. Schneider, M., Heimann, M., Schaub, C., et al.[2020]

Both craniotomy and stereotactic radiosurgery are effective treatment options for patients with limited brain metastases and favorable prognostic factors, suggesting that either method can be considered based on individual patient circumstances.

The study indicates that these two interventions may provide similar outcomes, allowing for flexibility in treatment planning for patients with specific clinical profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Radiosurgery in the Treatment of Brain Metastasis. Chin, HW., Rasp, G., Kim, J., et al.[2020]

Citations

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Advancements in Imaging and Neurosurgical Techniques ... Brain tumor surgery has witnessed significant advancements over the past few decades, resulting in improved patient outcomes.

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Effectiveness of craniotomy and long-term survival in 35 ... Our study showed that the mortality rate of patients who commenced chemotherapy more than 1 week after craniotomy was 31.6%, which was significantly higher than ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10527654/

Recent Advancements in the Surgical Treatment of Brain ... The surgical removal of brain tumors is essential for improving patient quality of life and survival. Recent advances in medical technology ...

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Presurgical predictors of early cognitive outcome after ... Most cognitive functions did not show significant worsening one week after surgery as compared to baseline before surgery.

5. hopkinsmedicine.org hopkinsmedicine.org/health/conditions-and-diseases/brain-tumor/brain-tumor-surgery

Brain Tumor Surgery Surgery is the first and most common treatment for most people with brain tumors. For some, surgical removal may be the only treatment needed.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10923735/

Optimizing patient outcome in intracranial tumor surgery The overall mortality rate stood at 0.8%, corresponding to five patient deaths. Causes of death included massive postoperative bleeding in one ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0967586822001655

Association between surgical volume and outcomes after ... High surgical volumes were associated with decreased 1-year all-cause mortality after craniotomy for brain tumor removal. However, since the type and stage of ...

8. upsurgeon.com upsurgeon.com/scientific-news/recognizing-surgical-complications-in-brain-tumor-resection/

Recognizing Surgical Complications in Brain Tumor ... Neurological deficits: Surgery in the brain carries the risk of causing neurological deficits, such as motor or speech dysfunction. · Infection: ...

9. link.springer.com link.springer.com/article/10.1007/s11060-024-04744-w

Neurosurgical resection of multiple brain metastases Perioperative complications were observed in 29.8% of cases, with transient complications occurring in 19.2% and permanent deficits in 10.6%.

10. mayoclinic.org mayoclinic.org/medical-professionals/neurology-neurosurgery/news/innovation-drives-brain-tumor-treatment/mac-20570354

Innovation drives brain tumor treatment Mayo Clinic applies the latest technical advancements to maximize the safety and outcomes of brain tumor resections.