Low vs Standard Dose Dexamethasone for Brain Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must be taking: Dexamethasone

Disqualifiers: CNS infection, Coagulopathy, Active malignancy, 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: 2

26 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies whether low dose dexamethasone works as well as standard dose dexamethasone to reduce brain swelling after brain surgery in patients with primary brain tumors or cancer that has spread from other places in the body to the brain (metastatic). Surgery is an important part of the treatment of brain tumors; however, it results in injury to surrounding brain tissue, leading to brain swelling. Dexamethasone is effective for controlling the swelling of the brain; however, dexamethasone can cause many unwanted side effects. To minimize the side effects of dexamethasone, the lowest dose needed to control swelling of the brain should be used. This research study is assessing the safety of using a lower than standard dose of dexamethasone after the surgery to control brain swelling.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you must be able to reduce your dexamethasone dose to 3 mg every 12 hours by 3 days before surgery to participate.

What data supports the effectiveness of the drug dexamethasone for brain cancer?

Research shows that dexamethasone can reduce brain tumor growth and improve quality of life in patients with brain metastasis by decreasing brain swelling. Lower doses of dexamethasone have been found to be as effective as higher doses, with fewer side effects. ^{1 2 3 4 5}

Is dexamethasone generally safe for humans?

Dexamethasone is generally safe for humans, but higher doses can lead to more side effects. Studies show that lower doses can be effective with fewer toxic effects, and it is commonly used to reduce brain swelling in cancer patients. ^{1 2 3 6 7}

How does the drug dexamethasone differ in low vs standard doses for brain cancer treatment?

The drug dexamethasone, when used in lower doses, can be as effective as the standard higher dose for treating brain cancer-related swelling, with fewer side effects. This makes it a potentially safer option for managing symptoms without compromising effectiveness. ^{3 5 6 8 9}

Research Team

Jana Portnow, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults over 18 with primary or metastatic brain tumors, able to reduce pre-surgery dexamethasone to a specified level and undergo complete tumor removal. They must have stable vital signs, no active infections or other cancers, and not be in another clinical trial.

Inclusion Criteria

My brain MRI shows less than 10 mm shift.

I have a brain tumor, either primary or metastatic.

I am taking more than 3 mg of dexamethasone every 12 hours but can reduce it to 3 mg before surgery.

Exclusion Criteria

I have a bleeding disorder or a condition that affects how my blood clots.

A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol

I have another active cancer besides the one being studied.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Treatment

Patients undergo brain surgery and receive dexamethasone (standard or low dose) before and after surgery

1 day

1 visit (in-person)

Post-operative Treatment

Patients receive dexamethasone (standard or low dose) for 14 days post-surgery, with tapering from day 4 to 14

14 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

Treatment Details

Interventions

• Dexamethasone

Trial Overview The study compares low versus standard doses of dexamethasone for reducing brain swelling post-surgery in patients with brain tumors. It aims to find the minimum effective dose that controls swelling while minimizing side effects.

Participant Groups

Group I: Arm II (lower dose dexamethasone) Experimental Treatment 1 Intervention

Patients receive lower dose dexamethasone PO q 12 h for 3 days. On the day of surgery, patients receive lower dose dexamethasone IV before and after the surgery. Patients receive lower dose dexamethasone IV q 12 h on days 1-3 post surgery and tapered dexamethasone PO q 12 h on days 4-14 in the absence of disease progression or unacceptable toxicity. Additional doses of dexamethasone are given if needed.

Group II: Arm I (standard dose dexamethasone) Active Control 1 Intervention

Patients receive standard dose dexamethasone PO q 12 h for 3 days. On the day of surgery, patients receive standard dose dexamethasone IV before and after the surgery. Patients receive standard dose dexamethasone IV q 12 h on days 1-3 post surgery and tapered dexamethasone PO q 12 h on days 4-14 in the absence of disease progression or unacceptable toxicity. Additional doses of dexamethasone are given if needed.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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 (Dex) significantly reduces the sensitivity of C6 glioma cells to methotrexate (MTX), allowing more cells to survive even at high concentrations of MTX.

This protective effect of Dex was also observed in human TE671 cells, indicating that the interaction between Dex and MTX is not limited to a specific species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. Wolff, JE., Jürgens, H.[2013]

References

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

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

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

Evidence-based dexamethasone dosing in malignant brain tumors: what do we really know? [2020]

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

Dose-effect relationship of dexamethasone on Karnofsky performance in metastatic brain tumors: a randomized study of doses of 4, 8, and 16 mg per day. [2021]

4. Scotland pubmed.ncbi.nlm.nih.gov

Dexamethasone for intracranial neurosurgery and anaesthesia. [2013]

5. Austria pubmed.ncbi.nlm.nih.gov

Therapeutic effects of topical dexamethasone on experimental brain tumours and peritumoural brain oedema. [2019]

6. Greece pubmed.ncbi.nlm.nih.gov

Dexamethasone induced partial resistance to methotrexate in C6-glioma cells. [2013]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Phase 1 Study to Evaluate the Safety of Reducing the Prophylactic Dose of Dexamethasone around Docetaxel Infusion in Patients with Prostate and Breast Cancer. [2023]

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

Twice-daily tapering dexamethasone treatment during cranial radiation for newly diagnosed brain metastases. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Dexamethasone treatment in patients with brain metastases and primary brain tumors: do the benefits outweigh the side-effects? [2022]