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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- Difference of Karnofsky performance status
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •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);
- •Expected survival of ≥ 3 months;
- •Having sufficient cognitive and understanding abilities, able to cooperate with scale assessments, and able to sign a written informed consent form (ICF);
- •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;
- •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.
排除标准
- •1. Immediate surgical decompression is required, or there may be progressive cerebral herniation, intracranial pressure crisis, or life-threatening intracranial space occupying lesions present;
- •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.);
- •Recent cranial surgery or radiation therapy (<4 weeks);
- •Individuals with contraindications to glucocorticoids or severe immunosuppression;
- •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;
- •Pregnant/lactating women;
- •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);
- •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;
- •Other serious systemic diseases or unsuitability.
研究组 & 干预措施
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.
干预措施: Methylprednisolone (Corticosteroid) (Drug)
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.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Difference of Karnofsky performance status
时间窗: within one week after radiotherapy
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
The incidence of adverse reactions related to hormone therapy
时间窗: From enrollment to 6 weeks after the end of radiotherapy
The incidence of adverse reactions related to hormone therapy (≥ grade 2);
次要结局
- Difference of Karnofsky performance status(before hormone use, start date of radiotherapy, 4-6 weeks after radiotherapy)
- Brain edema index (EI)(before hormone use, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy)
- Cognitive function changes(before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy)
- Quality of life changes(before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy)
- Treatment tolerability(From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy)
- Survival outcomes(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(From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy)
- Exploratory biomarker analysis(Baseline (first day of radiotherapy, prior to radiotherapy); and immediately after completion of radiotherapy (last day of radiotherapy).)