Post-Operative Dexamethasone for Brain Cancer

Overseen By Kimberly Hoang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: HPA dysfunction, Immunodeficiency, Lymphoma, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1-15 days

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests the effect of decreasing (tapering) doses of dexamethasone on steroid side effects in patients after surgery to remove (craniotomy) a brain tumor. Steroids are the gold standard post-surgery treatment to reduce swelling (edema) at the surgical site to reduce neurological symptoms. Although, corticosteroids reduce edema, they have side effects including high blood sugar, high blood pressure, and can impair wound healing. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response. It also works to treat other conditions by reducing swelling and redness. Tapering doses dexamethasone may decrease steroid side effects without increasing the risk of edema in patients with brain tumors after a craniotomy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking certain immunosuppressive drugs or have used high doses of corticosteroids recently.

What data supports the effectiveness of the drug Dexamethasone for post-operative brain cancer treatment?

Dexamethasone is commonly used to manage brain swelling and pressure in patients with brain tumors, and it is often given after surgery to help with these issues. It has been shown to reduce inflammation and complications after surgery in other types of cancer, like colorectal cancer. ^{1 2 3 4 5}

Is dexamethasone safe for use in humans?

Dexamethasone is generally safe for use in humans, but it can have side effects like diabetes, high blood pressure, and trouble sleeping. It is commonly used to manage brain swelling after surgery and to prevent nausea, but the dose and schedule can affect the risk of side effects. ^{1 3 4 6 7}

How does the drug dexamethasone differ from other treatments for brain cancer?

Dexamethasone is unique because it is a steroid used to reduce brain swelling and pressure after surgery for brain cancer, which helps manage symptoms like headaches and nausea. Unlike other treatments that directly target cancer cells, dexamethasone primarily addresses the complications associated with brain tumors, such as edema (swelling) and increased intracranial pressure. ^{1 2 3 7 8}

Research Team

Kimberly Hoang

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for adults over 18 who've had surgery to remove a brain tumor and have radiographic findings consistent with certain types of tumors. It's not for those under 18, pregnant women, people with specific immune or hormonal disorders, recent heavy corticosteroid use, or a history of solid organ transplant.

Inclusion Criteria

My brain scans show I might have a high-grade glioma, low-grade glioma, meningioma, or brain metastasis.

Exclusion Criteria

I am under 18 years old.

Pregnant women

I have lymphoma or leukemia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tapering doses of dexamethasone post-craniotomy, with blood sample collection and imaging as part of standard care

1-15 days

Daily visits during inpatient stay

Follow-up

Participants are monitored for safety and effectiveness, including neuropsychiatric assessments and wound checks

Up to 3 months

Follow-up visits at 2 weeks, 1 month, and 3 months

Wound Check

Optional wound check visit to assess healing and potential infections

10-14 days post-operative

1 optional visit

Treatment Details

Interventions

• Dexamethasone

Trial Overview The PODS Trial is testing whether decreasing doses of dexamethasone can reduce its side effects without increasing swelling risks after brain tumor surgery. The study involves CT scans, MRIs, biospecimen collection, and questionnaires to monitor outcomes.

Participant Groups

Group I: Arm II (RDS) Experimental Treatment 5 Interventions

Patients receive tapering doses of dexamethasone on days 1-4. Patients may receive dexamethasone IV and restart the taper if clinically indicated. Patients also undergo blood sample collection at time of surgery, follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo MRI and CT scan during inpatient stay as part of standard of care.

Group II: Arm I (NDS) Experimental Treatment 5 Interventions

Patients receive tapering doses of dexamethasone on days 1-15. Patients also undergo blood sample collection at time of surgery, at follow up visits and optionally at wound check visit 10-14 days post operative at investigator availability. Patients additionally undergo MRI and CT scan during inpatient stay as part of standard of care.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Dexamethasone is commonly used in patients with brain tumors undergoing neurosurgery to reduce inflammation and manage symptoms, highlighting its efficacy in this specific context.

The review also emphasizes the potential adverse effects of dexamethasone, which are important for both neurosurgeons and anesthetists to consider when administering this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone for intracranial neurosurgery and anaesthesia. Hockey, B., Leslie, K., Williams, D.[2013]

In glioblastoma patients, higher cumulative doses of dexamethasone in the first three postoperative weeks were linked to a 4% increase in mortality for every 16 mg increment, indicating potential risks associated with steroid use.

Increased dexamethasone administration also correlated with a 12% rise in the likelihood of continued steroid use and a 10% higher chance of developing infections, highlighting the need for careful management of dexamethasone in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of postoperative dexamethasone on survival, steroid dependency, and infections in newly diagnosed glioblastoma patients. Mistry, AM., Jonathan, SV., Monsour, MA., et al.[2022]

Dexamethasone is recommended for symptom relief in adult patients with primary high-grade gliomas and cerebral edema, with a maximum dose of 16 mg daily after surgery, divided into four doses.

While effective, dexamethasone can cause common side effects that worsen with higher doses and longer use, necessitating careful monitoring for various complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline. Kostaras, X., Cusano, F., Kline, GA., et al.[2021]

In a study of 480 patients undergoing elective colonic cancer surgery, higher doses of perioperative dexamethasone (4 mg and 8 mg) significantly reduced postoperative systemic inflammation and complications compared to no dexamethasone.

The combination of laparoscopic surgery and higher doses of dexamethasone was particularly effective in lowering postoperative complications, while the use of dexamethasone did not negatively affect cancer-specific or overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer. McSorley, ST., Dolan, RD., Roxburgh, CS., et al.[2020]

In a study of 515 rectal cancer patients, those who received perioperative dexamethasone had significantly lower three-year disease-free survival (62.3% vs 71.8%) and overall survival rates (74.1% vs 82.9%) compared to those who did not receive the drug.

The use of dexamethasone was independently associated with worse disease-free survival outcomes, suggesting that avoiding low-dose perioperative dexamethasone may improve survival for patients undergoing curative surgery for rectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer. Yu, HC., Luo, YX., Peng, H., et al.[2021]

The new reduced exogenous steroid taper (REST) protocol for dexamethasone after brain tumor surgery significantly decreased the incidence of new or worsened hypertension (0% in REST group vs. 20% in controls).

The REST protocol did not lead to increased length of stay or 30-day readmission rates, indicating it is a safe alternative to the traditional high-dose taper.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Reduced Exogenous Steroid Taper for Postoperative Brain Tumor Patients-A Case-Control Study. Breshears, JD., Haddad, AF., Viner, J., et al.[2019]

Dexamethasone is an effective synthetic steroid used for its anti-inflammatory, anti-allergic, and immunosuppressive properties, making it a valuable medication in various clinical settings.

It has been approved as a standard treatment for preventing and treating postoperative nausea and vomiting (PONV), highlighting its efficacy in managing side effects related to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Perioperative dexamethasone]. Sinner, B.[2021]

Dexamethasone (DEXA) effectively reduces glioma tumor growth in mice and rodents, with low concentrations inhibiting cell proliferation and higher concentrations inducing cell death, while also causing cellular stress responses in treated cells.

In human gliomas, DEXA shows variable effectiveness, with some cell lines resistant to its effects; however, DEXA does not harm normal brain cells, indicating its potential for neuroprotective effects while reducing tumor-induced damage and angiogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone alleviates tumor-associated brain damage and angiogenesis. Fan, Z., Sehm, T., Rauh, M., et al.[2021]

References

1. Scotland pubmed.ncbi.nlm.nih.gov

Dexamethasone for intracranial neurosurgery and anaesthesia. [2013]

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

Impact of postoperative dexamethasone on survival, steroid dependency, and infections in newly diagnosed glioblastoma patients. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Use of dexamethasone in patients with high-grade glioma: a clinical practice guideline. [2021]

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

Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer. [2020]

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

Avoiding perioperative dexamethasone may improve the outcome of patients with rectal cancer. [2021]

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

A Reduced Exogenous Steroid Taper for Postoperative Brain Tumor Patients-A Case-Control Study. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[Perioperative dexamethasone]. [2021]

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

Dexamethasone alleviates tumor-associated brain damage and angiogenesis. [2021]