A Study of Docetaxel Monotherapy or DOXIL and Docetaxel in Patients With Advanced Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is to evaluate whether the time to progression for the DOXIL and docetaxel combination therapy group was superior to that of the group treated with docetaxel monotherapy in participants with advanced breast cancer.

Detailed Description
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This is a randomized (the study medication is assigned by a random order), active control (study medication will be compared with available standard care of treatment), parallel-group (each treatment group will be treated simultaneously at the same time and each participant only receives one treatment regimen as assigned), open-label (both the investigator and the participant know the intervention received by the participant), multicenter study designed to determine if women with locally advanced or metastatic breast cancer, who were previously treated with prior anthracycline therapy in the neoadjuvant (administration of treatment before surgery) or adjuvant setting (administration of treatment after surgery), and who also had a disease-free interval of at least 12 months since the end of their last cytotoxic therapy, would benefit from the addition of DOXIL to docetaxel therapy. Approximately 751 participants will be randomly assigned to either receive docetaxel monotherapy or DOXIL in combination with docetaxel therapy. Treatment is to continue until disease progression or the occurrence of unacceptable treatment related toxicity. Safety evaluations will include assessments of adverse events which will be recorded from the first study related procedure until 30 days after the last dose of medication; clinical laboratory tests and tests for cardiac function (multiple gated acquisition scan/echocardiogram and electrocardiogram) which will be monitored throughout the study.

Official Title
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A Randomized Controlled Study of Docetaxel Monotherapy or Docetaxel and DOXIL for the Treatment of Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: DOXIL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females with locally advanced or metastatic breast cancer who received prior anthracycline therapy in the neoadjuvant or adjuvant setting, and had at least a 12-month disease-free interval since the end of their last cytotoxic therapy, were eligible for the study Participants who received prior hormonal therapy, or no more than 1 cytotoxic chemotherapy regimen (anthracyclines, taxanes, or antitubulin agents were not permitted), or both for advanced disease Participants with normal cardiac function, as evidenced by a normal left ventricular ejection fraction Exclusion Criteria: More than 1 prior cytotoxic chemotherapy regimen for advanced breast cancer Treatment of advanced breast cancer with an anthracycline, paclitaxel, docetaxel, vinorelbine, or vinblastine (prior treatment of advanced breast cancer with 1 regimen that included alkylating agents or antimetabolite agents was acceptable) Less than 2 months since the last dose of trastuzumab Less than 3 weeks since last dose of tamoxifen or fulvestrant, or less than 1 week since the last dose of other hormonal therapy Radiation to areas of disease within 30 days before study enrollment History of New York Heart Association Class II or greater cardiac disease or other clinical evidence of congestive heart failure

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: DOXIL and docetaxel combination therapy<br>DOXIL and docetaxel combination therapy: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. | Drug: Docetaxel<br>* Docetaxel monotherapy: docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. DOXIL in combination with docetaxel: docetaxel 60 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle<br>Drug: DOXIL<br>* DOXIL 30 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.<br>* Other names: DOXIL in combination with Docataxel;|
| Active Comparator: Docetaxel monotherapy<br>Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle | Drug: Docetaxel<br>* Docetaxel monotherapy: docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle. DOXIL in combination with docetaxel: docetaxel 60 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression | Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first. | From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time interval in months between the date of randomization and the participant's death from any cause. | From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled | 
| Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) | Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI). | Up to 30 to 42 days after last dose of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Advanced breast cancer, Breast Tumors, Cancer of Breast, Human Mammary Carcinoma, Mammary Neoplasms, Human, DOXIL, Docetaxel