Using corticosteroids to reduce hand–foot skin reactions from liposomal doxorubicin

The Role of Corticosteroids in Hand & Foot & Skin Reactions Reduction to Doxorubicin Liposomes

This study will test whether giving corticosteroids around doses of liposomal doxorubicin can reduce painful hand–foot skin reactions in people with breast cancer receiving AC chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 182 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, cyclophosphamide, doxorubicin
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07362914 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional protocol enrolls adults with early-stage or advanced breast cancer who are scheduled to receive the AC regimen (liposomal doxorubicin plus cyclophosphamide). Participants receive defined dexamethasone regimens alongside standard chemotherapy to compare skin toxicity outcomes. The trial incorporates correlative biomarker work based on preclinical data linking complement activation and neutrophil-mediated liposome uptake to cutaneous drug accumulation. Primary endpoints focus on the incidence and severity of hand–foot skin reactions and the need for dose reductions or treatment discontinuation.

Who should consider this trial

Good fit: Adults aged 18–70 with histologically confirmed breast cancer who are eligible for the AC regimen, have ECOG 0–1, anticipated survival ≥3 months, and meet specified blood and organ-function criteria.

Not a fit: Patients not receiving liposomal doxorubicin, those with contraindications to systemic corticosteroids, or those with poor performance status or insufficient organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, corticosteroid regimens could substantially lower hand–foot skin reactions, helping patients stay on planned liposomal doxorubicin therapy with fewer dose changes.

How similar studies have performed: Retrospective data from the sponsor center and preclinical complement-inhibition work suggest corticosteroids or complement blockade can reduce liposomal doxorubicin skin toxicity, but prospective randomized Phase 3 evidence is limited.

Eligibility criteria

Inclusion Criteria:

1. Patients aged 18-70 years (inclusive), regardless of gender.
2. Diagnosis \& Treatment Plan: Histopathologically confirmed early-stage or advanced breast cancer patients eligible for AC regimen (liposomal doxorubicin + cyclophosphamide) chemotherapy per clinical guidelines.
3. ECOG Performance Status: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
4. Anticipated survival ≥3 months.
5. Organ Function Requirements:

   Hematologic: Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L ,Platelet count ≥75 × 10⁹/L Hemoglobin ≥90 g/L

   Hepatic:

   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

   Renal:

   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
6. 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.
7. Informed Consent: Patients must voluntarily participate, provide signed informed consent, and comply with protocol-specified procedures (blood tests, follow-ups, etc.).

Exclusion Criteria:

1. 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).
2. Previous treatment with liposomal doxorubicin or similar formulations.
3. Allergy History: Known hypersensitivity to liposomal products or doxorubicin.
4. 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).
5. Active Infections: Grade ≥2 （NCI CTCAE v5.0）
6. Immunosuppression:

   Active autoimmune diseases, immunodeficiency (e.g., HIV-positive), or congenital/acquired immune disorders.

   History of organ transplantation or chronic corticosteroid use.
7. 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.
8. Other Infections: Positive for HCV antibody or syphilis-specific antibody.
9. Neurological/Psychiatric Disorders: History of epilepsy, dementia, or other uncontrolled conditions.
10. 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.
11. Any other condition that, per investigator assessment, may compromise patient safety or study compliance.
12. Pregnant or breastfeeding women.
13. Patients deemed ineligible for the study by the investigator.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jian Zhang, MD, PhD

Conditions Breast Cancer