Liposomal Doxorubicin (Lipo-Dox) in Patients With Brain Metastasis From Breast Cancer

A Phase II Study of Liposomal Doxorubicin (Lipo-Dox) in Patients With Brain Metastasis From Breast Cancer

Primary objective:

To determine the brain response rate of Lipo-Dox in breast cancer patients with brain metastasis

Secondary objectives:

1. To determine the overall objective response rate (ORR)
2. To determine the progression free survival, and duration of objective response
3. To evaluate the overall survival (OS)
4. To assess the safety profiles

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Liposomal Doxorubicin

Detailed Description

This is an open-label, non-comparative phase II clinical trial. Approximately thirty-three patients will be enrolled in order to obtain twenty-nine evaluable subjects who received two cycles of study treatment in Simon's 2-stage optimal design.

Duration of subject involvement: Study treatment should be administered up to disease progression, intolerable toxicity, or consent withdrawal.

Recruitment period: 10 months

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 308433
    • Johns Hopkins Singapore International Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically or cytologically proved breast cancer
• Relapse/recurrent brain metastasis progression after brain radiotherapy
• Presence of brain measurable disease which is defined as at least one brain lesion that can be measured in at least 1 dimension as ³ 20 mm with magnetic resonance image (MRI)
• Prior chemotherapy or hormone therapy for metastatic breast cancer is allowed
• Performance status of ECOG 0, 1, 2
• With normal left ventricular ejection fraction and normal ventricular contractility
• Age 21 years or older
• Life expectancy equal or longer than 3 months
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior anthracycline-containing chemotherapy with cumulative dose exceed 400mg/m2 doxorubicin or 750 mg/m2 Epirubicin
• Surgery , radiotherapy, hormonal therapy or chemotherapy within 4 weeks prior to entering the study
• Prior liposomal doxorubicin treatment
• Concurrent chemotherapy, radiotherapy, hormonal therapy, or other investigational drug except non-disease related conditions (e.g. insulin for diabetes) during study period
• Other malignancy with exception of curative treated non-melanoma skin cancer or cervical carcinoma in situ within 5 years prior to entering the study
• Brain metastases defined as meninges metastases

• Presence of serious concomitant illness which might be aggravated by study medication:

  • Uncontrolled infection (active serious infections that are not controlled by antibiotics)
  • Active cardiac disease e.g. decompensate myocardial infarction within the 6-month period preceding entry into the study.
  • History of ventricular arrhythmia or congestive heart failure.
• Presence of abnormal left ventricular ejection fraction

• Hematopoietic function as defined below:

  • Hemoglobin<10g/dl
  • ANC< 1,500/uL
  • Platelets<100,000/uL

• Organ function as defined below:

  • Total bilirubin >1.5 × ULN
  • ALT / AST>3 × ULN (>5.0 x ULN if hepatic metastasis)
  • Creatinine >1.5 × ULN
• Mental status is not fit for clinical trial
• Pregnant or breast feeding women, or women of child-bearing potential unless using a reliable and appropriate contraceptive method

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the brain response rate of Lipo-Dox in breast cancer patients with brain metastasis	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the overall objective response rate	3 years
To determine the progression free survival, and duration of objective response	3 years
To evaluate the overall survival	3 years
To assess the safety profiles	3 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: TTY Biopharm
• Investigators: Principal Investigator: Alex Chang, Johns Hopkins Singapore International Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: April 23, 2007
• First Submitted That Met QC Criteria: April 24, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Estimate): August 6, 2009
• Last Update Submitted That Met QC Criteria: August 4, 2009
• Last Verified: August 1, 2009

More Information

Terms related to this study

• Keywords: breast cancer; brain metastatsis; Lipo-Dox
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Breast Neoplasms; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: JS 0553