Brain Metastases From Solid Tumors
Conditions
Keywords
Brain metastases, Methylprednisolone, Dexamethasone, Peritumoral edema, Karnofsky performance status score, Biomarkers
Brief summary
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.
Interventions
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.
DRUGDexamethasone
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.
Sponsors
The Second Affiliated Hospital of Hainan Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Karnofsky performance status | 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 | From enrollment to 6 weeks after the end of radiotherapy | The incidence of adverse reactions related to hormone therapy (≥ grade 2); |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference of Karnofsky performance status | before hormone use, start date of radiotherapy, 4-6 weeks after radiotherapy | 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. |
| Brain edema index (EI) | before hormone use, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy | 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 |
| Cognitive function changes | before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy | 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) |
| Quality of life changes | before hormone use, start date of radiotherapy, within 1 week after radiotherapy, and 4-6 weeks after radiotherapy | 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 |
| Treatment tolerability | From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy | Differences in the incidence of radiotherapy interruption or delay (\>3 days) and the incidence of radiotherapy-related neurological adverse effects (RTOG grade ≥3) |
| 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. | including intracranial progression-free survival (PFS) and overall survival (OS) |
| Incidence of adverse events | From the first day of Glucocorticoidtherapy until 6 weeks after the end of radiotherapy | Incidence, severity (according to CTCAE v5.0), and correlation with the study drug of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs); |
| Exploratory biomarker analysis | Baseline (first day of radiotherapy, prior to radiotherapy); and immediately after completion of radiotherapy (last day of radiotherapy). | 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. |
Countries
China
Contacts
CONTACTyuecan zeng
CONTACTjunzhang chen
Outcome results
None listed