A Study of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Advanced and/or Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of intravenous (IV) trastuzumab (Herceptin) and IV docetaxel (Taxotere), with or without oral capecitabine (Xeloda), in women with previously untreated HER2-positive advanced and/or metastatic breast cancer.

Official Title
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An Open-Label, Randomized Phase II Study of Herceptin (Trastuzumab), Taxotere (Docetaxel), and Xeloda (Capecitabine) in Combination, Versus Herceptin (Trastuzumab) Plus Taxotere (Docetaxel), in Patients With Advanced and/or Metastatic Breast Cancers That Overexpress HER2

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Xeloda
* Drug: Taxotere
* Drug: Herceptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, HER2-positive advanced and/or metastatic breast cancer not amenable to curative therapy At least one measurable lesion according to RECIST Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Baseline left ventricular ejection fraction (LVEF) at least 50% Exclusion Criteria: Pregnant, lactating, or women of childbearing potential who are not surgically sterile or not willing to use adequate contraceptive methods Previous treatment with Herceptin or other anti-HER therapies, or any previous chemotherapy for advanced or metastatic disease Past medical history significant for any cardiac or central nervous system (CNS) disorders Poor hematologic, renal, or hepatic function Chronic corticosteroid therapy

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: Herceptin + Taxotere<br>Participants will receive dual therapy with Herceptin and Taxotere until disease progression, unmanageable toxicity, or withdrawal. | Drug: Taxotere<br>* Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm.<br>* Other names: docetaxel;Drug: Herceptin<br>* Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.<br>* Other names: trastuzumab;|
| Experimental: Herceptin + Taxotere + Xeloda<br>Participants will receive triple therapy with Herceptin, Taxotere, and Xeloda until disease progression, unmanageable toxicity, or withdrawal. | Drug: Xeloda<br>* Participants will receive oral Xeloda, 950 mg/m^2 twice a day on Days 1 to 14 of each 21-day cycle.<br>* Other names: capecitabine;Drug: Taxotere<br>* Participants will receive Taxotere, 75 milligrams per meter-squared (mg/m^2) in the Herceptin + Taxotere + Xeloda arm or 100 mg/m^2 in the Herceptin + Taxotere arm, via IV infusion on Day 1 of each 21-day cycle. The lower starting dose will be used in the triple-therapy arm.<br>* Other names: docetaxel;Drug: Herceptin<br>* Participants will receive Herceptin, 6 milligrams per kilogram (mg/kg) via IV infusion, on Day 1 of each 21-day cycle. The first dose will be a loading dose of 8 mg/kg in Cycle 1; the dose of 6 mg/kg will be given from Cycle 2 onward.<br>* Other names: trastuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) | Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a best overall response for CR or PR was reported. The exact 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper method. | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Death or Disease Progression According to RECIST | Tumor response was assessed by RECIST during the study. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. The percentage of participants who died or experienced PD was reported. | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | 
| Progression-Free Survival (PFS) According to RECIST | Tumor response was assessed by RECIST during the study. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. PFS was defined as the time from start of treatment to the first event of death or PD. Participants without event at the time of analysis were censored at the latest date of last tumor assessment or last date in drug log. The median duration of PFS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) | 
| Percentage of Participants Who Died | The percentage of participants who died from any cause was reported. | Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall) | 
| Overall Survival (OS) | OS was defined as the time from start of treatment to date of death for any reason. Participants who were alive at the time of analysis were censored at the latest date of last tumor assessment, last drug intake, or last follow-up information. The median duration of OS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. | Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall) | 
| Duration of Response (DOR) According to RECIST | Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as ≥30% decrease in sum LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. DOR was defined as the time from first assessment of CR or PR until the first occurrence of documented PD, death, or withdrawal. The median DOR was reported and expressed in months. | Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall) |