The Role of Corticosteroids in Hand & Foot & Skin Reactions Reduction to Doxorubicin Liposomes
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 182
- 试验地点
- 1
- 主要终点
- Number of participants with hand-foot syndrome (HFS) as assessed by CTCAE v5.0 in the high-dose dexamethasone group
研究概览
简要总结
Investigating the Association Between Corticosteroid Use and Improvement in Doxorubicin Liposome-Induced Cutaneous Toxicity: Exploring the Feasibility and Mechanisms of Corticosteroids in Mitigating Liposomal Doxorubicin-Related Dermatologic Adverse Effects.
详细描述
Background
Liposomal doxorubicin exhibits distinct toxicity profiles compared to free-form doxorubicin in clinical practice. Cutaneous toxicity represents the primary dose-limiting adverse effect of liposomal doxorubicin, with incidence and severity demonstrating a dose-dependent relationship . Current management strategies-including dose reduction or extended treatment intervals-yield limited efficacy, often leading to treatment discontinuation due to intolerable symptoms, thereby compromising clinical utility.
Mechanistic Insights
Our preliminary research identified neutrophils as key mediators in liposomal skin accumulation:
Complement receptor 3 (CR3) recognizes iC3b deposited on liposomes via complement activation.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged 18-70 years (inclusive), regardless of gender.
- •Diagnosis & Treatment Plan: Histopathologically confirmed early-stage or advanced breast cancer patients eligible for AC regimen (liposomal doxorubicin + cyclophosphamide) chemotherapy per clinical guidelines.
- •ECOG Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or
- •Anticipated survival ≥3 months.
- •Organ Function Requirements:
- •Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L ,Platelet count ≥75 × 10⁹/L Hemoglobin ≥90 g/L
- •Non-liver metastasis: Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN Liver metastasis: TBIL ≤1.5 × ULN ,ALT and AST ≤5 × ULN
- •Serum creatinine (Cr) ≤1.5 × ULN or creatinine clearance (Ccr) ≥50 mL/min
- •Coagulation:
- •International normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN Activated partial thromboplastin time (APTT) ≤1.5 × ULN
- •Contraception:
- •Female patients: Must use effective contraception (e.g., intrauterine device [IUD], oral contraceptives, or condoms) during the study and for 6 months after study completion. A negative serum pregnancy test within 7 days prior to enrollment is required, and patients must be non-lactating.
- •Male patients: Must agree to use contraception during the study and for 6 months after study completion.
- •Informed Consent: Patients must voluntarily participate, provide signed informed consent, and comply with protocol-specified procedures (blood tests, follow-ups, etc.).
排除标准
- •Received chemotherapy, radiotherapy, biologics, targeted therapy, immunotherapy, or other antitumor treatments within 4 weeks before the first study dose (or within 5 half-lives, whichever is shorter). Exceptions: The washout period may be adjusted per investigator judgment (e.g., shortened to 2 weeks for endocrine therapy to avoid prolonged patient waiting).
- •Previous treatment with liposomal doxorubicin or similar formulations.
- •Allergy History: Known hypersensitivity to liposomal products or doxorubicin.
- •Cardiovascular Diseases:
- •Severe arrhythmias/conduction abnormalities (e.g., clinically significant ventricular arrhythmias, second- or third-degree AV block).
- •History of myocardial infarction, coronary artery bypass grafting (CABG), or heart failure (NYHA Class ≥II).
- •LVEF ≤50%or prolonged QTcF (>450 ms in males; >470 ms in females).
- •Active Infections: Grade ≥2 （NCI CTCAE v5.0）
- •Immunosuppression:
- •Active autoimmune diseases, immunodeficiency (e.g., HIV-positive), or congenital/acquired immune disorders.
- •History of organ transplantation or chronic corticosteroid use.
- •HBsAg-positive with HBV-DNA ≥500 IU/mL. Exception: If HBV-DNA <500 IU/mL and chronic hepatitis is deemed stable/inactive by the investigator, enrollment is permitted.
- •Other Infections: Positive for HCV antibody or syphilis-specific antibody.
- •Neurological/Psychiatric Disorders: History of epilepsy, dementia, or other uncontrolled conditions.
- •CNS Metastases: Symptomatic brain or leptomeningeal metastases, or uncontrolled CNS lesions. Exception: Asymptomatic brain metastases or lesions stable for ≥28 days without steroids/antitumor therapy are allowed.
- •Any other condition that, per investigator assessment, may compromise patient safety or study compliance.
- •Pregnant or breastfeeding women.
- •Patients deemed ineligible for the study by the investigator.
研究组 & 干预措施
Arm A(NEO-DXMS GROUP)
no dexamethasone
干预措施: Doxorubicin hydrochloride liposome injection (Drug)
Arm A(NEO-DXMS GROUP)
no dexamethasone
干预措施: Cyclophosphamide (Drug)
Arm B( MED-DEX GROUP )
dexamethasone 12mg d1, PO/IV
干预措施: Dexamethasone (12mg d1) (Drug)
Arm B( MED-DEX GROUP )
dexamethasone 12mg d1, PO/IV
干预措施: Doxorubicin hydrochloride liposome injection (Drug)
Arm B( MED-DEX GROUP )
dexamethasone 12mg d1, PO/IV
干预措施: Cyclophosphamide (Drug)
Arm C(HIGH-DEX GROUP )
dexamethasone 12mg QD, d1-5, PO/IV
干预措施: Dexamethasone (2mg QD, d1-5,) (Drug)
Arm C(HIGH-DEX GROUP )
dexamethasone 12mg QD, d1-5, PO/IV
干预措施: Doxorubicin hydrochloride liposome injection (Drug)
Arm C(HIGH-DEX GROUP )
dexamethasone 12mg QD, d1-5, PO/IV
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Number of participants with hand-foot syndrome (HFS) as assessed by CTCAE v5.0 in the high-dose dexamethasone group
时间窗: 17 months
Compared to both the no-dexamethasone group and the standard-dose dexamethasone group, the high-dose dexamethasone group demonstrated reduced incidence of hand-foot syndrome (HFS)
次要结局
- Overall survival (OS)(17 months)
- ncidence of Treatment-Emergent Adverse Events(17 months)
- Disease-free survival (DFS)(17 months)
- Progression-free survival (PFS)(17 months)
研究者
Jian Zhang,MD
Chief Physician
Fudan University