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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing dexamethasone doses, a common steroid used after brain tumor surgery, can lower harmful side effects like high blood sugar and high blood pressure while still preventing brain swelling. Participants will follow different tapering schedules of dexamethasone to determine the most effective approach. It suits individuals who have undergone surgery to remove a brain tumor, such as gliomas or meningiomas, and are experiencing steroid-related side effects. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research shows that dexamethasone, a commonly used steroid, reduces swelling after brain surgery by decreasing fluid buildup, which relieves pressure in the brain. However, it can also cause side effects such as high blood sugar, high blood pressure, and wound healing issues.

Studies suggest that adjusting the dose of dexamethasone after surgery might lessen these side effects without increasing swelling. Some research has found that using dexamethasone before and after surgery might raise the risk of wound infections. Concerns also exist that using steroids during surgery could lead to complications within the first 30 days post-surgery.

In summary, while dexamethasone effectively manages swelling, finding the right dose is crucial to minimize side effects. This trial explores how adjusting the dose might help achieve that balance. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about the use of dexamethasone for post-operative brain cancer care because it offers a potentially quicker and more flexible approach to managing inflammation and swelling compared to traditional treatments. Unlike other corticosteroids, dexamethasone can be administered in tapering doses immediately after surgery, allowing for personalized adjustments based on the patient's clinical needs. This adaptability might improve recovery times and reduce side effects, which is why there's a buzz around its potential benefits in post-operative settings.

What evidence suggests that tapering doses of dexamethasone might be an effective treatment for reducing steroid side effects in brain cancer patients post-surgery?

Research shows that dexamethasone is commonly used to control swelling around brain tumors. In this trial, participants will receive tapering doses of dexamethasone, with Arm I (NDS) receiving doses on days 1-15 and Arm II (RDS) on days 1-4. Studies have found that lower doses of dexamethasone after brain tumor surgery can effectively manage swelling. However, higher doses might be linked to worse outcomes, such as shorter survival times. Lower doses aim to reduce swelling while minimizing side effects like high blood sugar and high blood pressure. These studies suggest that gradually reducing the dose could provide benefits without increasing the risk of complications after surgery. ^{2 5 6 7 8}

Who Is on the Research Team?

Kimberly Hoang

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 (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]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2832545

Practice Variation in Perioperative Dexamethasone Use ... The findings of this study suggest that variations in perioperative dexamethasone dosing across centers may affect outcomes and stricter dosing protocols ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/?term=40214989

Practice Variation in Perioperative Dexamethasone Use ... In this study, higher cumulative perioperative dexamethasone was associated with reduced OS, icPFS, and ecPFS in patients undergoing brain metastasis resection.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12406498/

Dexamethasone in brain tumor patients - PubMed Central - NIH Dexamethasone is routinely prescribed for the management of peritumoral edema in brain tumor patients. Despite available orientations for ...

4. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii174/7889733

INNV-25. POST-OPERATIVE LOW DOSE VERSUS ... Administration of lower doses of dexamethasone post-operatively to brain tumor patients with mild to moderate cerebral edema is feasible.

5. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1153392/full

Association between intraoperative steroid and ... In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11074443/

The safety and use of perioperative dexamethasone in the ... The present study evaluates the effect of dexamethasone on postoperative complications, peritumoral T2/FLAIR hyperintensity, and progression-free survival

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06132685

Post-Operative Dosing of Dexamethasone in Patients with ... Tapering doses dexamethasone may decrease steroid side effects without increasing the risk of edema in patients with brain tumors after a craniotomy. Detailed ...

8. thejns.org thejns.org/view/journals/j-neurosurg/136/4/article-p1062.xml

The safety and efficacy of dexamethasone in the perioperative ... CONCLUSIONS. Combined pre- and postoperative dexamethasone use may increase the risk of postoperative wound infection, and dexamethasone use, ...