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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding brain tumors by analyzing their glucose usage, a type of sugar, during surgery. The researchers aim to create a detailed picture of the tumor's behavior and link it to its genetic makeup. The trial involves surgical resection, using a special kind of glucose to gather this information. Suitable participants are those recently diagnosed with a brain tumor and planning surgical removal. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future brain tumor treatments.

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 prior data suggests that this surgical resection technique is safe?

Research has shown that surgery to remove brain tumors is usually well-tolerated. In past studies, surgeons used tools like MRI scans during operations to safely remove more of the tumor. This method made the surgery more effective in about 30% of cases. However, risks exist, such as the chance of a stroke during surgery, especially when the tumor is near critical brain areas. Surgery plays a key role in brain cancer treatment and is often combined with other treatments like radiation and chemotherapy to extend patients' lives. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this surgical resection for brain cancer because it involves a unique approach that could enhance tumor removal precision. Unlike standard surgical techniques, this method includes the infusion of 13C-glucose before surgery, which may help in better identifying tumor boundaries. This innovative combination of advanced imaging and surgical navigation could potentially improve surgical outcomes and reduce the risk of leaving cancerous tissue behind.

What evidence suggests that surgical resection is effective for brain cancer?

Research has shown that surgery to remove a brain tumor can be effective. In this trial, participants will undergo surgical resection of a brain tumor. When surgeons remove the entire visible tumor, known as gross total resection (GTR), patients may live longer—sometimes up to 20-25 months. This is especially true for fast-growing brain cancers like glioblastoma. Undergoing surgery sooner can also lead to better outcomes. Overall, removing more of the tumor can improve the chances of extended survival. ^{6 7 8 9 10}

Who Is on the Research Team?

Elizabeth Maher, MD, PhD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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]

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]

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]

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]

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 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]

Citations

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Timing of glioblastoma surgery and patient outcomes Patients with tumor volumes > 50 mL with more than a month of time-to-surgery appear to have lower extent of resection and shorter survival and could be ...

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Surgical efficacy and survival outcomes of fluorescein ... This study demonstrates that FS-guided surgery significantly improves GTR and reduces the proportion of residual tumor tissue compared to conventional WL ...

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Comparing Glioblastoma Surgery Decisions Between ... Nevertheless, the prognosis remains dismal, with a 1-year survival rate of 39%. Initial neuro-oncologic treatment decisions include whether to ...

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Supramaximal Resection for Glioblastoma When gross total resection (GTR) is achieved, patient survival may extend to 20–25 months [2]. For glioma resection, including GBM, the goal is ...

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Association of the Extent of Resection With Survival ... The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies.

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Maximal Safe Resection in Glioblastoma Surgery The mean survival rate is 12–15 months following the gold-standard treatment, including maximal safe resection, radiation therapy, and adjuvant chemotherapy [2 ...

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Efficacy and safety of intraoperative MRI in glioma surgery Intraoperative MRI led to extended glioma resections in 29.2% of the investigated pooled data, aligning with rates from other studies: 35.2% in ...

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Risk factors and prognostic implications of surgery-related ... We explored the incidence, risk factors and clinical consequences of intra-operative ischemic strokes in surgeries for resection of HGG.