Comparison of the Therapeutic Effects of Methylprednisolone and Dexamethasone on Peritumoral Edema During Radiotherapy for Brain Metastases:

Comparison of the Therapeutic Effects of Methylprednisolone and Dexamethasone on Peritumoral Edema During Radiotherapy for Brain Metastases:An Adaptive Phase II/III Seamless Prospective Clinical Study

This study is a multicenter, open label, randomized controlled, adaptive phase II/III seamless design clinical trial aimed at comparing the efficacy and safety of methylprednisolone (MP) and dexamethasone (DEX) in the treatment of peritumoral edema in patients with brain metastases during radiotherapy. The research plan includes brain metastasis patients aged 18-75 years, with KPS scores of 40-80, who plan to undergo whole brain radiotherapy or stereotactic radiotherapy. They will be randomly divided into MP group (40-60 mg/day) or DEX group (8-12 mg/day) in a 1:1 ratio, and medication will be continued until the end of radiotherapy, followed by gradual reduction and cessation within one week. The study is divided into two stages: the first stage (stage II exploration) includes 120 cases to preliminarily evaluate the efficacy and safety, and provide a basis for re estimating the sample size in the second stage; The second stage (Phase III confirmation) will expand the sample size based on the results after analysis during the transition period, with a total sample size of no more than 400 cases. The primary endpoint was the change in KPS score and the incidence of grade ≥ 2 hormone related adverse reactions within one week after radiotherapy. Secondary endpoints include cerebral edema index, cognitive function, quality of life, radiotherapy interruption rate, neurotoxicity, survival, and serum biomarkers (IL-6, S100B). The study is supervised by an independent data security monitoring committee and uses statistical methods such as stratified block randomization and mixed effects models to ensure the scientific and ethical compliance of the data. This study is expected to provide high-level evidence-based basis for hormone selection during the perioperative radiotherapy period for patients with brain metastases, and optimize clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Brain Metastases From Solid Tumors
• Intervention / Treatment: Drug: Methylprednisolone (Corticosteroid); Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: yuecan zeng; Phone Number: 19946610752; Email: wellyy2005@hainmc.edu.cn
• Study Contact Backup: Name: junzhang chen; Phone Number: 13189068479; Email: chenjz0824@163.com

Study Locations

• China
  • Hainan
    • Haikou, Hainan, China, China 570311
      • The Second Affiliated Hospital of Hainan Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. 18 ≤ age ≤ 75 years old, gender not limited, generally acceptable, 40 ≤ KPS ≤ 80 points, the main reason for the patient's limited functional status is related neurological symptoms caused by edema of brain metastases; 2. Confirmed by cranial MRI or CT imaging, there is at least one brain metastasis with cerebral edema or neurological symptoms. All patients are scheduled to undergo WBRT (30 Gy/10f or 20 Gy/5f) or SBRT (20-40 Gy/1-6f, with ≤ 5 brain metastases and a maximum diameter of ≤ 5cm per lesion); 3. Expected survival of ≥ 3 months; 4. Having sufficient cognitive and understanding abilities, able to cooperate with scale assessments, and able to sign a written informed consent form (ICF); 5. Baseline neurological symptoms are stable (no need for emergency surgical decompression), and if surgery/radiotherapy has been performed, the following conditions must be met: postoperative/radiotherapy interval ≥ 4 weeks; 6. Baseline blood glucose/metabolism is controllable (e.g., HbA1c ≤ 8.0% in diabetes patients;If HbA1c is high, endocrinology evaluation is required and written permission for enrollment is granted.

Exclusion Criteria:

• 1. Immediate surgical decompression is required, or there may be progressive cerebral herniation, intracranial pressure crisis, or life-threatening intracranial space occupying lesions present; 2. Has received systemic corticosteroid treatment within 7 days prior to the start of the study medication (such as due to the treatment of systemic lupus erythematosus, bronchial asthma, etc.); 3. Recent cranial surgery or radiation therapy (<4 weeks); 4. Individuals with contraindications to glucocorticoids or severe immunosuppression; 5. Suffering from serious basic diseases such as uncontrolled hypertension and diabetes (HbA1c>8%), untreated mental illness, active gastric ulcer, heart failure (NYHA III-IV grade), etc; 6. Pregnant/lactating women; 7. Unable to complete the primary assessment scale (severe cognitive/behavioral impairment) or unable to sustain Follow up period (e.g. no fixed address, difficult to ensure follow-up); 8. Participated in other intervention therapy trials within the past 4 weeks (which may affect the evaluation results), or is currently receiving drugs that may have serious drug interactions with the investigational drug; 9. Other serious systemic diseases or unsuitability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group（Methylprednisolone）; Methylprednisolone group regimen: The total daily dose is 40-60 mg (oral or intravenous), starting from the diagnosis of brain metastasis and continuing until the end of radiotherapy. Subsequently, the dosage is gradually reduced by 20-50% of the total dose, and complete discontinuation is achieved within one week.	Drug: Methylprednisolone (Corticosteroid); The total daily dose is 40-60 mg (oral or intravenous), starting from the diagnosis of brain metastasis and continuing until the end of radiotherapy. Subsequently, the dosage is gradually reduced by 20-50% of the total dose, and complete discontinuation is achieved within one week.
Active Comparator: Control group（Dexamethasone）; The dosing regimen for the dexamethasone group is: a total daily dose of 8-12 mg (oral or intravenous), starting from the diagnosis of brain metastasis and continuing until the end of radiotherapy. Subsequently, the dosage is gradually reduced by 20-50% of the total dose, and complete discontinuation is achieved within one week.	Drug: Dexamethasone; The total daily dose is 8-12 mg (oral or intravenous), starting from the diagnosis of brain metastasis and continuing until the end of radiotherapy. Subsequently, the dosage is gradually reduced by 20-50% of the total dose, and complete discontinuation is achieved within one week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of Karnofsky performance status	The difference in Karnofsky performance status within one week after radiotherapy compared to baseline value;The minimum and maximum values are 0 and 100 points respectively, and the higher the score, the better the patient's health condition	within one week after radiotherapy
The incidence of adverse reactions related to hormone therapy	The incidence of adverse reactions related to hormone therapy (≥ grade 2);	From enrollment to 6 weeks after the end of radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference of Karnofsky performance status	Differences in Karnofsky performance status changes at different time points during the perioperative radiotherapy period (before hormone use, start date of radiotherapy, 4-6 weeks after radiotherapy)；The minimum and maximum values are 0 and 100 points respectively, and the higher the score, the better the patient's health condition.	before hormone use, start date of radiotherapy, 4-6 weeks after radiotherapy
Brain edema index (EI)	Using cranial MRI to detect the differences in changes in cerebral edema index (EI) at different time points during the perioperative radiotherapy period (before hormone use, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy) in patients	before hormone use, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy
Cognitive function changes	The Montreal Cognitive Assessment Scale (MoCA) was used to evaluate the differences in cognitive function at different time points during the perioperative radiotherapy period (before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy)	before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy
Quality of life changes	Evaluate the differences in quality of life between two groups of patients at different time points during the perioperative radiotherapy period (before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy) using the QOL scale	before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy
Treatment tolerability	Differences in the incidence of radiotherapy interruption or delay (>3 days) and the incidence of radiotherapy-related neurological adverse effects (RTOG grade ≥3)	From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy
Survival outcomes	including intracranial progression-free survival (PFS) and overall survival (OS)	For intracranial progression-free survival (PFS): assessed at baseline, then every 3 months until disease progression, up to 2 years; For overall survival (OS): assessed at baseline, then every 3 months until death from any cause, up to 2 years.
Incidence of adverse events	Incidence, severity (according to CTCAE v5.0), and correlation with the study drug of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs);	From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy
Exploratory biomarker analysis	Dynamically monitor serum IL-6 and S100B levels to analyze the correlation between changes in their serum levels and the occurrence and severity of radiotherapy-induced neurotoxicity.	Baseline (first day of radiotherapy, prior to radiotherapy); and immediately after completion of radiotherapy (last day of radiotherapy).

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Hainan Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 15, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: April 6, 2026
• First Submitted That Met QC Criteria: April 14, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Dexamethasone; Methylprednisolone; Brain metastases; Peritumoral edema; Karnofsky performance status score
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Prednisolone; Dexamethasone; Methylprednisolone; Adrenal Cortex Hormones
• Other Study ID Numbers: 2026-K04-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No