Surgical Resection for Brain Cancer

Overseen By Omar Raslan, MBBCH,MPH, CCRP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Claustrophobia, Pacemaker, Congestive heart failure, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 14

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is designed to use infusion of a non-radioactive, naturally occurring isotope of glucose (13C) in patients undergoing surgical resection for a newly identified brain mass to obtain the metabolic phenotype of the tumor, and correlate it with the histopathological diagnosis. In each patient, 13C NMR spectral analysis of tumor extracts will be obtained after intraoperative infusion of \[U-13C\]glucose or \[1,2-13C\]glucose. Whenever feasible, patients will undergo 3 preoperative imaging studies - 18FDG-PET, diffusion tensor imaging with 1H-spectroscopy on 3T MR scanner, and ultra high resolution MR imaging on the 7T MR scanner. The results of these imaging studies will be correlated with the metabolic phenotype to generate a comprehensive non-invasive view of the tumor with the goal of identifying infiltrative, metabolically active tumor cells within the brain. In addition, a comprehensive molecular profile of the tumor will be obtained and enable a genotype-metabolic phenotype comparative analysis. Correlative Translational Research The investigators will obtain tumor tissue from each patient for comprehensive molecular analysis (array CGH, expression profiling, methylation profiling) which will be correlated with tumor histology, the metabolites identified by 1H-MR spectroscopy and the 13Cglucose metabolic profile. Patients will be followed at designated time points along their treatment course to obtain information about ongoing treatment and response, time to tumor progression and overall survival. These parameters will be used in correlational analysis with the metabolic phenotype.

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 Surgical Resection for Brain Cancer?

Research shows that surgical resection (removal of the tumor) of brain metastases can improve survival and quality of life, especially when combined with other treatments like stereotactic radiosurgery (a precise form of radiation therapy). This approach has been shown to improve local control of the cancer and increase overall survival rates. ^{1 2 3 4 5}

Is surgical resection for brain cancer generally safe in humans?

The research articles provided do not directly address the safety of surgical resection for brain cancer. They focus on the safety of combining other treatments like stereotactic radiosurgery and immune therapies for brain metastases from different cancers. ^{5 6 7 8 9}

How does the treatment Surgical Resection differ from other treatments for brain cancer?

Surgical Resection for brain cancer involves physically removing the tumor, which can improve survival and reduce recurrence, especially when combined with advanced techniques like image-guided neurosurgery. This approach is different from non-surgical treatments like stereotactic radiosurgery, which uses focused radiation to target the tumor without removing it. ^{1 10 11 12 13}

Research Team

Elizabeth Maher, MD, PhD

Principal Investigator

University of Texas

Eligibility Criteria

This trial is for individuals of any age with a brain tumor, who can consent to the study or have a guardian who can. They must not be pregnant, should be in relatively good health (Karnofsky Performance status > 70%), and able to undergo MRI scans unless they have certain medical devices or severe claustrophobia.

Inclusion Criteria

My gender, age, and ethnicity do not limit my eligibility.

I am mostly independent and can care for myself.

I am not pregnant and cannot become pregnant due to surgery, menopause, or I use two forms of birth control.

Exclusion Criteria

Women of childbearing potential who refuse a pregnancy test (performed during screening)

I need assistance with my daily activities.

I have severe heart failure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Imaging

Participants undergo preoperative imaging studies including 3T MRI with DTI and 1H-MR spectroscopy, 7T MRI, and 18FDG-PET scan

1-2 weeks

1 visit (in-person)

Surgical Resection and Infusion

Participants undergo surgical resection of the tumor after infusion of 13C-glucose and/or 13C-acetate

1 day

1 visit (in-person)

Postoperative Follow-up

Participants are assessed for adverse events 10-14 days after surgery

2 weeks

1 visit (in-person)

Long-term Follow-up

Participants are monitored every 6 months for 5 years for treatment response, tumor progression, and overall survival

5 years

10 visits (virtual or in-person)

Treatment Details

Interventions

• Surgical Resection

Trial Overview The trial involves surgical removal of the brain tumor while also studying its metabolism using a special form of glucose during surgery. The metabolic profile will be compared with high-resolution imaging before surgery and molecular analysis after, aiming to better understand the tumor's characteristics.

Participant Groups

Group I: surgical resection of a brain tumor Experimental Treatment 1 Intervention

The patient will undergo surgical removal of the tumor after infusion of 13C-glucose using standard neurosurgical technique, including frameless stereotaxy for surgical navigation, and microsurgical technique. --------------------------------------------------------------------------------

Surgical Resection is already approved in United States, European Union for the following indications:

Approved in United States as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial carcinoma
• Esophageal carcinoma
• Gastric cancer

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Endometrial carcinoma
• Esophageal carcinoma
• Gastric cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

Surgical resection of brain metastases can significantly improve survival rates, reduce local recurrence, and enhance functional independence for patients with up to three metastases and controlled systemic disease.

Advancements in surgical techniques, such as minimally invasive approaches and intraoperative mapping, allow for safer procedures that help preserve normal brain function during the removal of tumors located in critical areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Techniques for Open Surgical Resection of Brain Metastases. Wang, JL., Elder, JB.[2021]

In a study of 222 patients with large brain metastases from non-small-cell lung cancer, multi-fraction stereotactic radiosurgery (mfSRS) alone showed comparable overall survival rates to surgery followed by mfSRS, with median survival times of 13.5 months and 15.2 months respectively.

Patients receiving mfSRS alone experienced significantly lower rates of radiation-induced brain necrosis (7%) compared to those who underwent surgery followed by mfSRS (15%), suggesting that mfSRS alone may be a safer option for managing large brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of multi-fraction stereotactic radiosurgery for surgically resected or intact large brain metastases from non-small-cell lung cancer (NSCLC). Minniti, G., Scaringi, C., Lanzetta, G., et al.[2020]

In a study of 57 patients with multiple brain metastases, minimally invasive neurosurgical techniques led to significant improvements in patient quality of life, with 80.6% of patients showing improvement in their Karnofsky Performance Status (KPS) at 6 weeks post-surgery.

The mean overall survival for these patients was 14.2 months, with a 1-year survival rate of 44%, indicating that while surgery can improve outcomes, factors like cancer control and extent of resection significantly influence survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally invasive key-hole approach for the surgical treatment of single and multiple brain metastases. Gazzeri, R., Nalavenkata, S., Teo, C.[2014]

Adjuvant stereotactic radiosurgery (SRS) significantly improves local control of resected brain metastases, with a median overall survival of 1.5 years for 282 patients studied.

Delays in starting SRS after surgery negatively impact its effectiveness, with a marked increase in surgical site recurrence rates when SRS is initiated more than 2 months post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. Bander, ED., Yuan, M., Reiner, AS., et al.[2022]

In a study of 116 patients with surgically resected brain metastases, about one-third (41 patients) were found to be suitable for stereotactic radiosurgery (SRS), which could provide a less invasive treatment option compared to traditional surgery.

Patients whose tumors were suitable for SRS had a median overall survival of 7.7 months, compared to 5.4 months for those not suitable, suggesting that SRS may offer a potential survival benefit while also reducing hospital stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is stereotactic radiosurgery under-utilised in the treatment of surgically excisable cerebral metastases? Lee, MK., Javadpour, M., Jenkinson, MD.[2018]

In a safety cohort study of 13 patients with non-small cell lung cancer and brain metastasis, concurrent stereotactic radiosurgery (SRS) with immune checkpoint inhibitors nivolumab and ipilimumab was found to be safe, with only one patient experiencing a dose-limiting toxicity.

The estimated 4-month intracranial progression-free survival rate was 70.7%, suggesting that this combination therapy may be effective in treating brain metastases from NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial. Altan, M., Wang, Y., Song, J., et al.[2023]

In a study of 30 patients with KRAS-mutated non-small cell lung cancer and brain metastases, sotorasib showed varying effectiveness based on the status of brain metastases, with a median intracranial progression-free survival of 15 months for patients with stable brain metastases, compared to only 3 months for those with active metastases without recent local therapy.

Although sotorasib demonstrated some intracranial activity, 57% of patients experienced progression, highlighting the need for a comprehensive treatment approach for brain metastases and suggesting that further research with larger cohorts is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief report on the efficacy of sotorasib in KRAS-Mutated NSCLC patients with brain metastases. Lebouille-Veldman, AB., Taros, TN., Nawabi, NLA., et al.[2023]

In a study of 54 patients with newly diagnosed melanoma brain metastases, combining ipilimumab with stereotactic radiosurgery (SRS) did not lead to increased rates of radiation necrosis or hemorrhage, indicating that this combination is safe.

Despite the safety of the combination treatment, there were no significant improvements in overall survival or local control when comparing ipilimumab plus SRS to SRS alone, suggesting that ipilimumab may not enhance treatment outcomes in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Stereotactic Radiosurgery Versus Stereotactic Radiosurgery Alone for Newly Diagnosed Melanoma Brain Metastases. Patel, KR., Shoukat, S., Oliver, DE., et al.[2022]

In a phase II trial involving 26 patients with brain metastases from non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), combining nivolumab with stereotactic radiosurgery (SRS) resulted in a one-year intracranial progression-free survival (iPFS) rate of 45.2%, indicating promising efficacy for this treatment approach.

The combination treatment was well tolerated, with only two patients experiencing grade 3 fatigue, and quality of life scores significantly improved, suggesting that SRS with nivolumab not only controls tumor growth but also enhances patient well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicenter trial combining nivolumab and radiosurgery for NSCLC and RCC brain metastases. Wong, P., Masucci, L., Florescu, M., et al.[2023]

In a study analyzing resection margin tissue from metastatic tumors, no tumor cells were found infiltrating the surrounding brain tissue, indicating a clear boundary after gross total resection.

This finding suggests that stereotactic radiosurgery can be safely targeted to a narrow depth of the resection cavity margin, potentially reducing damage to normal brain tissue and minimizing complications associated with larger treatment areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metastasis infiltration: an investigation of the postoperative brain-tumor interface. Raore, B., Schniederjan, M., Prabhu, R., et al.[2011]

Supratotal resection (SpTR) for glioblastoma (GBM) significantly improves overall survival and progression-free survival compared to other surgical methods, based on a meta-analysis of 13 retrospective studies.

The analysis showed a hazard ratio of 0.77 for overall survival and 0.20 for progression-free survival, indicating that SpTR is a more effective surgical approach for patients with GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis. Aziz, PA., Memon, SF., Hussain, M., et al.[2023]

Aggressive surgical resection of metastatic brain tumors has been shown to improve survival rates in patients, highlighting the importance of timely intervention.

Advancements in surgical techniques, such as preoperative imaging and image-guided surgery, have reduced the risks associated with these procedures, leading to lower morbidity and mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of brain metastases. Weinberg, JS., Lang, FF., Sawaya, R.[2019]

A systematic review and meta-analysis of 614 patients with solitary brain metastases found no significant differences in overall survival (OS) or local recurrence (LR) between surgical resection (SR) and stereotactic radiosurgery (SRS).

The analysis highlighted high heterogeneity among studies and suggested that various significant co-variables may influence outcomes, indicating a need for further research to explore different metrics beyond OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical resection versus stereotactic radiosurgery on local recurrence and survival for patients with a single brain metastasis: a systematic review and meta-analysis. González, L., Castro, S., Villa, E., et al.[2022]

References

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

Techniques for Open Surgical Resection of Brain Metastases. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of multi-fraction stereotactic radiosurgery for surgically resected or intact large brain metastases from non-small-cell lung cancer (NSCLC). [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Minimally invasive key-hole approach for the surgical treatment of single and multiple brain metastases. [2014]

4. England pubmed.ncbi.nlm.nih.gov

Durable 5-year local control for resected brain metastases with early adjuvant SRS: the effect of timing on intended-field control. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Is stereotactic radiosurgery under-utilised in the treatment of surgically excisable cerebral metastases? [2018]

6. England pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab with concurrent stereotactic radiosurgery for intracranial metastases from non-small cell lung cancer: analysis of the safety cohort for non-randomized, open-label, phase I/II trial. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Brief report on the efficacy of sotorasib in KRAS-Mutated NSCLC patients with brain metastases. [2023]

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

Ipilimumab and Stereotactic Radiosurgery Versus Stereotactic Radiosurgery Alone for Newly Diagnosed Melanoma Brain Metastases. [2022]

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

Phase II multicenter trial combining nivolumab and radiosurgery for NSCLC and RCC brain metastases. [2023]

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

Metastasis infiltration: an investigation of the postoperative brain-tumor interface. [2011]

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

Supratotal Resection: An Emerging Concept of Glioblastoma Multiforme Surgery-Systematic Review And Meta-Analysis. [2023]

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

Surgical management of brain metastases. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Surgical resection versus stereotactic radiosurgery on local recurrence and survival for patients with a single brain metastasis: a systematic review and meta-analysis. [2022]