A Study to Assess Capecitabine (Xeloda®) in Patients With Locally Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This 2 arm study compared the efficacy and safety of label dose of capecitabine (Xeloda®) to that of a lower dose of Xeloda® plus docetaxel (Taxotere®) in patients with locally advanced or metastatic breast cancer after failure of chemotherapy with an anthracycline. Patients were randomized to receive either 1250 mg/m^2 or 825 mg/m^2 orally twice a day (po bid) on days 1-14 of each 3 week cycle, in combination with Taxotere® 75 mg/m2 intravenous (iv) on day 1 of each 3 week cycle. The anticipated time on study treatment was until disease progression and the target sample size was 440 individuals.

Official Title
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A Randomized, Open-label Study of the Effect of Different Dosing Regimens of Xeloda® in Combination With Taxotere® on Disease Progression in Patients With Locally Advanced and/or Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine (Xeloda®)
* Drug: docetaxel (Taxotere®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women >=18 years of age; >=1 target lesion; locally advanced or metastatic breast cancer; demonstrated resistance to anthracycline; >=2 regimens of chemotherapy for advanced/metastatic disease. Exclusion Criteria: previous treatment with Xeloda, continuous 5-fluorouracil infusion, or other oral fluoropyrimidines; previous treatment with paclitaxel or docetaxel for advanced/metastatic disease.

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: 1250 mg/m^2 capecitabine + docetaxel<br>1250 mg/m^2 capecitabine (Xeloda®) orally twice a day on days 1 to 14 of each 3 week cycle, in combination with docetaxel (Taxotere®) 75 mg/m^2 intravenous on day 1 of each 3 week cycle. | Drug: capecitabine (Xeloda®)<br>* 825 mg/m^2 or 1250 mg/m2 orally twice a day on days 1 to 14 of each 3 week cycle.<br>* Other names: Xeloda®;Drug: docetaxel (Taxotere®)<br>* 75 mg/m^2 intravenous on day 1 of each 3 week cycle<br>* Other names: Taxotere®;|
| Experimental: 825 mg/m^2 capecitabine + docetaxel<br>825 mg/m^2 capecitabine orally twice a day on days 1 to 14 of each 3 week cycle, in combination with docetaxel 75 mg/m^2 intravenous on day 1 of each 3 week cycle. | Drug: capecitabine (Xeloda®)<br>* 825 mg/m^2 or 1250 mg/m2 orally twice a day on days 1 to 14 of each 3 week cycle.<br>* Other names: Xeloda®;Drug: docetaxel (Taxotere®)<br>* 75 mg/m^2 intravenous on day 1 of each 3 week cycle<br>* Other names: Taxotere®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression of Disease or Death | Progression Free Survival was defined as the time from the date of randomization to the day of documented disease progression or death due to any cause. | Event driven (after 350 events). Median observation time was approximately 16 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Best Overall Response Being Complete Response (CR) or Partial Response (PR) | According to Response Evaluation Criteria in Solid Tumors (RECIST) criteria: CR is defined as the disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the nadir sum LD. | Until Progressive Disease (PD) or end of primary study treatment (up to 16 cycles) plus 28 days. | 
| Time to Overall Response | For patients with Best Overall Response being Complete Response (CR) or Partial Response (PR), time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR were met. The percentage of participants with overall response within the given time ranges in each of the categories: Weeks 1-6, 7-12, 13-18, 19-24, 25-30, 31-36, and 43-48 are reported. | Until PD or end of primary study treatment (up to 16 cycles) plus 28 days. | 
| Duration of Overall Response | Duration of overall response was measured from the time that measurement criteria were first met for Complete Response or Partial Response until the first date that progressive disease or death was documented. | Until PD or death. Median duration of response was approximately 7 months. | 
| Time to Treatment Failure | The time to treatment failure was the time from the date of randomization to the first occurrence of any of the following events: adverse events insufficient therapeutic response (disease progression) death failure to return refusing treatment/being unwilling to cooperate withdrawing consent. | Until premature withdrawal or end of primary study treatment (up to 16 cycles). | 
| Overall Survival | Overall Survival was measured as the time from the date of randomization to the date of death. | Throughout the study. Median observation time was approximately 16 months. | 
| Number of Participants With Adverse Events and Serious Adverse Events | An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is Life-Threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Additional information about Adverse Events can be found in the Adverse Event Section. | First study drug intake until last study drug intake plus 28 days |