A Study of Pegylated Liposomal Doxorubicin and Cyclophosphamide in Her2-negative Stage I and II Breast Cancer Patients

Study Overview
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Brief Summary
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Primary objective: To evaluate the disease-free survival (DFS) in the two randomized arms after therapy with LC vs. EC in chemo-naive Her2-patients with stage I or II breast cancer Secondary objectives: To assess the overall survival (OS) To establish the safety profile by assessing the toxicities and tolerability To assess the quality of life (QoL) To evaluate survival correlation with biomarkers expression.

Official Title
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A Phase II Randomized Study of Pegylated Liposomal Doxorubicin, Cyclophosphamide Versus Epirubicin-Cyclophosphamide as Adjuvant Chemotherapy in Her2-negative Stage I and II Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Epirubicin+Cyclophosphamide
* Drug: liposomal-doxorubicin+Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed invasive, but non-inflammatory, breast adenocarcinoma with stage I or II (if N0, T must be >1cm) disease Her2-negative on fluorescence in situ hybridization (FISH) study performance status of ECOG 0, 1 female, age between 20 and 70 years life expectancy of at least one year ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Her2 3+ over-expression on immunohistochemistry (IHC), or Her2 amplification on fluorescence in situ hybridization (FISH) study previous or current systemic malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, unless there has been a disease-free interval of at least 5 years Patients who have received prior chemotherapy inadequate hematological function defined as absolute neutrophil count (ANC)less than 1,500/mm3, and platelets less than 100,000/mm3 inadequate hepatic function defined as: serum bilirubin greater than 1.5 times the upper limit of normal range (ULN) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the ULN inadequate renal function defined as serum creatinine greater than 1.5 times the ULN left ventricular ejection fraction (LVEF) < 50% confirmed by multiple-gated acquisition (MUGA) scan or echocardiogram concomitant illness that might be aggregated by chemotherapy or interfere study assessment. For examples, active, non- controlled infection (such as hepatitis B and hepatitis C, HIV, infectious tuberculosis) or other active, non-controlled disease such as congestive heart failure, ischemic heart disease, uncontrolled hypertension or arrhythmia, unstable diabetes mellitus, and active peptic ulcer patients who are presence of liver cirrhosis or are HBV/HCV carrier participation in another clinical trial with any investigational drug within 30 days prior to entry pregnant or breast feeding women fertile women of child-bearing potential unless using a reliable and appropriate contraceptive method throughout the treatment period and for three months following cessation of treatment

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: EC<br>Cyclophosphamide,600 mg/m2 q3wk and Epirubicin,90 mg/m2 q3wk | Drug: Epirubicin+Cyclophosphamide<br>* Cyclophosphamide 600 mg/m2 infusion followed by epirubicin 90 mg/m2 infusion on Day 1 in each 21-day treatment cycle. Treatment will be repeated for 4 cycles in the EC arm.<br>|
| Experimental: LC<br>liposomal doxorubicin, 37.5 mg/m2 q3wk, and Cyclophosphamide,600 mg/m2 q3wk | Drug: liposomal-doxorubicin+Cyclophosphamide<br>* Cyclophosphamide 600 mg/m2 infusion followed by pegylated liposomal-doxorubicin 37.5mg/m2 infusion on Day 1 in each 21-day treatment cycle. Treatment will be repeated for 5 cycles in the LC arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | To evaluate the disease-free survival (DFS) in the two randomized arms after therapy with LC vs. EC in chemo-naive Her2-patients with stage I or II breast cancer | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 
| Quality of life |  | Baseline and every 3 weeks during therapy | 
| Safety profiles | Incidence and severity of adverse event (neutropenia, palmar-plantar erythrodysesthesia, cardiac function, and secondary leukemia) by assessing the toxicities and tolerability | 5 years | 
| Survival correlation with biomarkers expression |  | At approximately of 5 years maximum FU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase II, Pegylated Liposomal Doxorubicin, Adjuvant Chemotherapy, Breast Cancer