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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Epirubicin+Cyclophosphamide; Drug: liposomal-doxorubicin+Cyclophosphamide

• Study Type: Interventional
• Enrollment (Anticipated): 254
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Changhua, Taiwan
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Linkou, Taiwan
    • Chang-Gung Memorial Hospital, Linkou
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Shin Kong Wu Ho-Su Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: EC; Cyclophosphamide,600 mg/m2 q3wk and Epirubicin,90 mg/m2 q3wk	Drug: Epirubicin+Cyclophosphamide; 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.
Experimental: LC; liposomal doxorubicin, 37.5 mg/m2 q3wk, and Cyclophosphamide,600 mg/m2 q3wk	Drug: liposomal-doxorubicin+Cyclophosphamide; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TTY Biopharm
• Investigators: Principal Investigator: Ming-Feng Hou, MD, Kaohsiung Medical University Chung-Ho Memorial Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: August 31, 2010
• First Submitted That Met QC Criteria: September 27, 2010
• First Posted (Estimate): September 28, 2010

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 22, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer; Phase II; Pegylated Liposomal Doxorubicin; Adjuvant Chemotherapy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Epirubicin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: TTYLD0914