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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00338286

Enrollment

2098

Registered

2006-06-20

Start date

2006-03-02

Completion date

2017-01-31

Last updated

2018-03-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer, Neoplasm Metastasis

Keywords

anemia, metastatic breast cancer, Hemoglobin, progression-free survival (PFS), erythropoiesis-stimulating agents (ESA)

Brief summary

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

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.

Interventions

OTHERStandard supportive care (packed RBC transfusion)

Per doctor prescription

DRUGepoetin alfa + packed RBC transfusion

40,000 IU SC once a week.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 99 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Progression Free Survival	From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years)	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.

Secondary

Measure	Time frame	Description
Overall Survival	From randomization up to death from any cause (up to 8.4 years)	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.
Time to Tumor Progression	From date of randomization to the date of the first documented PD (up to 8.4 years)	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).
Overall Response Rate (ORR)	every 8 weeks for 1 year and then every 12 weeks until PD or death, whichever occurred first (up to 8.4 years)	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.
Percentage of Participants With Suspected Thrombotic Vascular Events (TVEs)	up to 8.4 years	Suspected TVEs were identified by investigators and relevant clinical information was collected.

Countries

Argentina, Brazil, Bulgaria, Chile, Colombia, Ecuador, Georgia, Hong Kong, India, Indonesia, Malaysia, Mexico, North Macedonia, Philippines, Poland, Romania, Russia, South Africa, Taiwan, Ukraine, United States

Participant flow

Pre-assignment details

Participants in safety data were grouped as treatment actually received (3 were assigned to SOC but received epoetin alfa; 2 were assigned to EPO, but received SOC) so, 1 more to EPO (1051) 1 less in SOC (1045) actually received treatment. Efficacy, safety were analyzed by 1050 (EPO), 1048 (SOC), 1051 (EPO), 1045 (SOC) respectively.

Participants by arm

Arm	Count
Standard Supportive Care (SOC) Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	1,048
Epoetin Alfa Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.	1,050
Total	2,098

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Lost to Follow-up	80	66
Overall Study	Other	103	93
Overall Study	Withdrawal by Subject	50	54

Baseline characteristics

Characteristic	Standard Supportive Care (SOC)	Epoetin Alfa	Total
Age, Continuous	51.8 years STANDARD_DEVIATION 10.54	51.9 years STANDARD_DEVIATION 10.49	51.9 years STANDARD_DEVIATION 10.51
Region of Enrollment ARGENTINA	4 Participants	5 Participants	9 Participants
Region of Enrollment BRAZIL	27 Participants	16 Participants	43 Participants
Region of Enrollment BULGARIA	14 Participants	10 Participants	24 Participants
Region of Enrollment CHILE	11 Participants	13 Participants	24 Participants
Region of Enrollment COLOMBIA	3 Participants	1 Participants	4 Participants
Region of Enrollment ECUADOR	1 Participants	1 Participants	2 Participants
Region of Enrollment GEORGIA	241 Participants	200 Participants	441 Participants
Region of Enrollment HONG KONG	1 Participants	0 Participants	1 Participants
Region of Enrollment INDIA	211 Participants	237 Participants	448 Participants
Region of Enrollment INDONESIA	4 Participants	5 Participants	9 Participants
Region of Enrollment MACEDONIA	4 Participants	5 Participants	9 Participants
Region of Enrollment MALAYSIA	7 Participants	6 Participants	13 Participants
Region of Enrollment MEXICO	8 Participants	12 Participants	20 Participants
Region of Enrollment PHILIPPINES	60 Participants	54 Participants	114 Participants
Region of Enrollment ROMANIA	0 Participants	3 Participants	3 Participants
Region of Enrollment RUSSIA	102 Participants	129 Participants	231 Participants
Region of Enrollment TAIWAN	19 Participants	30 Participants	49 Participants
Region of Enrollment UKRAINE	328 Participants	318 Participants	646 Participants
Region of Enrollment UNITED STATES OF AMERICA	3 Participants	5 Participants	8 Participants
Sex: Female, Male Female	1048 Participants	1050 Participants	2098 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	883 / 1,045	898 / 1,051
serious Total, serious adverse events	229 / 1,045	251 / 1,051

Outcome results

Primary

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.

Time frame: From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years)