Clinical trial NCT00338286: A Study of Epoetin Alfa Plus Standard Supportive Care Versus Standard Supportive Care Only in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Neoplasm Metastasis
Keywords: anemia
metastatic breast cancer
Hemoglobin
progression-free survival (PFS)
erythropoiesis-stimulating agents (ESA)
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2006-06-20
Enrollment: 2098
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years)
Secondary outcomes:
measure: Overall Survival
timeFrame: From randomization up to death from any cause (up to 8.4 years)
measure: Time to Tumor Progression
timeFrame: From date of randomization to the date of the first documented PD (up to 8.4 years)
measure: Overall Response Rate (ORR)
timeFrame: every 8 weeks for 1 year and then every 12 weeks until PD or death, whichever occurred first (up to 8.4 years)
measure: Percentage of Participants With Suspected Thrombotic Vascular Events (TVEs)
timeFrame: up to 8.4 years
Other outcomes:
Locations:
city: Anaheim
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: New Port Richey
country: United States
state: Florida
city: Rockledge
country: United States
state: Florida
city: Hazard
country: United States
state: Kentucky
city: Alexandria
country: United States
state: Louisiana
city: Marrero
country: United States
state: Louisiana
city: Jackson
country: United States
state: Mississippi
city: Lake Success
country: United States
state: New York
city: Staten Island
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Corpus Christi
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Buenos Aires
country: Argentina
city: Capital Federal
country: Argentina
city: Ciudad Autonoma De Buenos Airess
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Mendoza
country: Argentina
city: Quilmes
country: Argentina
city: Rosario
country: Argentina
city: Santa Fe
country: Argentina
city: Barretos
country: Brazil
city: Curitiba
country: Brazil
city: Goiânia/Go
country: Brazil
city: Ijuí
country: Brazil
city: Jau
country: Brazil
city: Piracicaba
country: Brazil
city: Porto Alegre
country: Brazil
city: Ribeirão Preto/Sp
country: Brazil
city: Santo Andre
country: Brazil
city: Sao Paulo
country: Brazil
city: São José Do Rio Preto
country: Brazil
city: São Paulol
country: Brazil
city: Plovdiv
country: Bulgaria
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Varna
country: Bulgaria
city: Arica
country: Chile
city: Santiago
country: Chile
city: Temuco
country: Chile
city: Valdivia
country: Chile
city: Valparaiso
country: Chile
city: Bogota
country: Colombia
city: Floridablanca-Santander
country: Colombia
city: Monteria
country: Colombia
city: Cuenca
country: Ecuador
city: Guayaquil
country: Ecuador
city: Portoviejo
country: Ecuador
city: Quito
country: Ecuador
city: Batumi
country: Georgia
city: Tbilisi
country: Georgia
city: Tblisi
country: Georgia
city: New Territories
country: Hong Kong
city: Ahmedabad
country: India
city: Andra Pradesh
country: India
city: Bangalore N/A
country: India
city: Bangalore
country: India
city: Bhopal
country: India
city: Cochin
country: India
city: Delhi
country: India
city: Hyderabad
country: India
city: Jaipur
country: India
city: Karnad
country: India
city: Kerala
country: India
city: Kolkata
country: India
city: Mangalore
country: India
city: Mumbai
country: India
city: Nashik
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Tamil Nadu Na
country: India
city: Tamil Nadu
country: India
city: Thiruvananthapuram
country: India
city: Uttar Pradesh
country: India
city: Vellore
country: India
city: Bandung
country: Indonesia
city: Jakarta
country: Indonesia
city: Semarang
country: Indonesia
city: Yogyakarta
country: Indonesia
city: Bitola
country: Macedonia, The Former Yugoslav Republic of
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
city: Georgetown
country: Malaysia
city: Kelantan
country: Malaysia
city: Kuala Lumpur
country: Malaysia
city: Nilai
country: Malaysia
city: Tanjung Bunga
country: Malaysia
city: Chihuahua
country: Mexico
city: Guerrero
country: Mexico
city: Leon
country: Mexico
city: Merida
country: Mexico
city: Morelia
country: Mexico
city: Puebla
country: Mexico
city: San Luis Potosi
country: Mexico
city: Sinaloa
country: Mexico
city: Zapopan
country: Mexico
city: Cebu
country: Philippines
city: Davao City
country: Philippines
city: Iloilo City
country: Philippines
city: Manila
country: Philippines
city: Quezon City
country: Philippines
city: Białystok
country: Poland
city: Gdansk
country: Poland
city: Gliwice
country: Poland
city: Katowice N/A
country: Poland
city: Kraków
country: Poland
city: Lodz
country: Poland
city: Olsztyn
country: Poland
city: Poznan
country: Poland
city: Wroclaw
country: Poland
city: Brasov
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Onesti
country: Romania
city: Sibiu
country: Romania
city: Suceava
country: Romania
city: Timisoara
country: Romania
city: Arkhangelsk
country: Russian Federation
city: Balashikha
country: Russian Federation
city: Belgorod
country: Russian Federation
city: Chelyabinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Engels Saratov Region
country: Russian Federation
city: Ivanovo
country: Russian Federation
city: Kazan
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Leningrad Region
country: Russian Federation
city: Lipetsk
country: Russian Federation
city: Magnitogorsk
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Obninsk
country: Russian Federation
city: Orenburg
country: Russian Federation
city: Perm
country: Russian Federation
city: Pyatigorsk
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Smolensk
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Ufa
country: Russian Federation
city: Voronezh
country: Russian Federation
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Durban
country: South Africa
city: Johannesburg
country: South Africa
city: Klerksdorp
country: South Africa
city: Port Elizabeth N/A
country: South Africa
city: Pretoria
country: South Africa
city: Changhua
country: Taiwan
city: Chiayi
country: Taiwan
city: Hualien
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taichung
country: Taiwan
city: Tainan
country: Taiwan
city: Taipei 112
country: Taiwan
city: Taipei
country: Taiwan
city: Tao-Yuan
country: Taiwan
city: Cherkassy
country: Ukraine
city: Chernihiv
country: Ukraine
city: Chernivtsi
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Ivano-Francovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kiev
country: Ukraine
city: Lviv
country: Ukraine
city: Odessa
country: Ukraine
city: Poltava
country: Ukraine
city: Sumy
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Vinnitsa
country: Ukraine
city: Vinnytsia
country: Ukraine
city: Zaporozhye
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC C. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Leyland-Jones B, Bondarenko I, Nemsadze G, Smirnov V, Litvin I, Kokhreidze I, Abshilava L, Janjalia M, Li R, Lakshmaiah KC, Samkharadze B, Tarasova O, Mohapatra RK, Sparyk Y, Polenkov S, Vladimirov V, Xiu L, Zhu E, Kimelblatt B, Deprince K, Safonov I, Bowers P, Vercammen E. A Randomized, Open-Label, Multicenter, Phase III Study of Epoetin Alfa Versus Best Standard of Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy. J Clin Oncol. 2016 Apr 10;34(11):1197-207. doi: 10.1200/JCO.2015.63.5649. Epub 2016 Feb 8.