A Study of Epoetin Alfa Plus Standard Supportive Care Versus Standard Supportive Care Only in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the impact on tumor progression as evaluated by progression-free survival (PFS) of epoetin alfa plus standard supportive care as compared with standard supportive care alone (packed red blood cell (RBC) transfusions), for treating anemia according to label guidance in patients with metastatic breast cancer receiving standard chemotherapy.

Detailed Description
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Anemia is a common complication of the treatment of metastatic breast cancer and is related to the effects of chemotherapy and to chronic disease itself. This is a randomized, open-label, multicenter, international study to further examine the safety of the study drug used with standard supportive care (i.e., packed RBC transfusions) compared to standard supportive care alone, when used to treat anemia associated with chemotherapy. This study will be done in subjects with metastatic breast cancer who are being or will be treated with first-line chemotherapy with standard dose schedules of taxane monotherapy, or a taxane plus trastuzumab, or an anthracycline plus either a taxane or cyclophosphamide. The study hypothesis is that epoetin alfa, when used as supportive anemia care, does not increase the risk of tumor progression or death. The study treatment will be compared to the control treatment by comparing progression-free survival, i.e., the number of months from the date a patient is randomized into the trial to the date of the first documented disease progression or death. In addition to their chemotherapy, half of the subjects will be assigned to receive study drug (epoetin alfa) and half of the subjects will be assigned to standard supportive care for anemia. Subjects treated with the study drug will receive standard supportive care (packed RBC transfusions) plus 40,000 IU epoetin alfa given subcutaneously once a week until 4 weeks after the last cycle of chemotherapy or until disease progression, whichever comes first.The hypothesis is to test that epoetin alfa, when used as supportive anemia care, is non-inferior to control (standard supportive care alone), as measured by progression free survival (PFS). Patients treated with the study drug will receive standard supportive care (packed red blood cells (RBC) transfusions) plus 40,000 IU epoetin alfa given subcutaneously once a week until 4 weeks after the last cycle of chemotherapy or until disease progression, whichever comes first. Dose adjustments (dose escalation, dose reduction, dose interruption, and dose resumption) of epoetin alfa will be based on hemoglobin (Hb) and confirm to prescribing information.

Official Title
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A Randomized, Open-label, Multicenter, Phase 3 Study of Epoetin Alfa Plus Standard Supportive Care Versus Standard Supportive Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy

Conditions
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Breast Cancer, Neoplasm Metastasis

Intervention / Treatment
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* Other: Standard supportive care (packed RBC transfusion)
* Drug: epoetin alfa + packed RBC transfusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed (e.g., slide of tissue) breast cancer HER2/NEU positive or negative Clinical evidence of metastasis (e.g., biopsy) with at least 1 measurable metastatic (M1) lesion prior to starting the current chemotherapy Received 1st and 2nd line chemotherapy Hemoglobin (Hb) <= 11g/dL at the time of randomization planned to receive at least 2 more cycles of chemotherapy Life expectancy > 6 months Eastern Cooperative Oncology Group score 0 or 1 At least 18 years old using effective birth control or surgically sterile or postmenopausal for 1 year Exclusion Criteria: Active second cancer no recent history of clinically relevant thrombovascular event Current treatment with anticoagulants Brain metastasis or CNS involvement Anemia secondary to another cause Recent (within prior 1 months) use of an ESA Patient pregnant or breast feeding Progressive disease during adjuvant/neoadjuvant chemotherapy Rapidly progressive or life-threatening metastatic disease Concomitant endocrine therapy Patient in whom the only site of metastasis was local and was successfully treated surgically.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: 001<br>epoetin alfa + packed RBC transfusion 40 000 IU SC once a week. | Drug: epoetin alfa + packed RBC transfusion<br>* 40,000 IU SC once a week.<br>|
| Other: 002<br>Standard supportive care (packed RBC transfusion) Per doctor prescription | Other: Standard supportive care (packed RBC transfusion)<br>* Per doctor prescription<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival was based in investigator-determined progressive disease (PD) and calculated from the date of randomization to the date of PD or the date of death, whichever occurred first. Participants who had not progressed and were still alive at the time of clinical cut off were censored at the last disease assessment prior to the clinical cutoff. For PD or death with a missing interval immediately preceding the event, progression-free survival (PFS) was censored at the last disease assessment prior to the missing interval. Participants who withdrew from the study (withdrawal of consent or lost to follow-up) without progression were censored at the time of the last disease assessment. | From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival (OS) was defined as the interval between the date of randomization to the date of death from any cause. For participants who were lost to follow-up or withdrew before the final database lock, OS was censored at the last date the participants was known to be alive. For participants who were still alive and on study at the time of the final database lock, OS was censored at the date of final database lock. | From randomization up to death from any cause (up to 8.4 years) | 
| Time to Tumor Progression | The Time to tumor progression (TTP) was defined as the time from the date of starting treatment until the date of first documented evidence of progression of tumor. TTP was measured from the date of randomization to the date of the first documented PD (including death due to PD without prior PD). | From date of randomization to the date of the first documented PD (up to 8.4 years) | 
| Overall Response Rate (ORR) | Overall response was RECIST criteria. Complete response (CR) is appearance of all target and non-target lesions. Partial response (PR):a) 30% decrease in sum of lactate dehydrogenase(LD) of target lesions from baseline OR b) complete disappearance of target lesions, with persistence of one or more non-target measurable lesion or one or more non-measurable, evaluable lesions. Progressive disease(PD):a) 20% increase in sum of LDs of target lesions, taking as reference smallest sum LD recorded since treatment started; OR b) appearance of one or more new lesions or a clear worsening of measurable non-target lesions or evaluable disease with stable measurable lesions. Stable disease (SD):a) sufficient shrinkage to qualify for PR;b) sufficient increase to qualify for PD. Non evaluable(NE) lesion: all other lesions, including small lesions (longest diameter <20 millimeter (mm) with conventional techniques or <10 mm with spiral CT scan) and truly non-measurable lesions. | every 8 weeks for 1 year and then every 12 weeks until PD or death, whichever occurred first (up to 8.4 years) | 
| Percentage of Participants With Suspected Thrombotic Vascular Events (TVEs) | Suspected TVEs were identified by investigators and relevant clinical information was collected. | up to 8.4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, metastatic breast cancer, Hemoglobin, progression-free survival (PFS), erythropoiesis-stimulating agents (ESA)