A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT02107703
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either abemaciclib + fulvestrant or fulvestrant alone. Participants will be randomized to abemaciclib or placebo in a 2:1 ratio. The study will last about 9 months for each participant.
For the endocrine naïve cohort, all participants will received abemaciclib + fulvestrant.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 669
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Abemaciclib + Fulvestrant Fulvestrant Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Placebo + Fulvestrant Placebo Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Abemaciclib + Fulvestrant Abemaciclib Abemaciclib 150 milligram (mg) administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met. Placebo + Fulvestrant Fulvestrant Placebo administered orally every 12 hours on Days 1 to 28 of a 28-day cycle in combination with fulvestrant 500mg administered IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants received treatment until discontinuation were met.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 31 Months) PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 31 Months) DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Percentage of Participants Achieving CR, PR or Stable Disease (SD) (Disease Control Rate [DCR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Percentage of Participants With CR, PR or SD With a Duration of At Least 6 Months (Clinical Benefit Rate [CBR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) Clinical benefit rate defined as percentage of participants with best overall response of CR, PR, or SD with a duration of at least 6 months.CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions.PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Percentage of participants=(participants with CR+PR+SD with a duration of at least 6 months /number of participants enrolled) \*100.PD was at least a 20% increase in sum of the diameters of target lesions,with reference being the smallest sum on study and an absolute increase of at least 5 mm or unequivocal progression of non-target lesions,or 1 or more new lesions.
Change From Baseline in Pain and Symptom Burden Assessment Using the Modified Brief Pain Inventory-Short Form (mBPI-sf) Baseline, End of Study (Up To 31 Months) A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). The overall change is based on the estimated main treatment effect. Least square (LS) Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Overall Survival (OS) From Date of Randomization until Death Due to Any Cause (Up To 72 Months) OS defined as the time from the date of randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. The final analysis of the OS outcome was conducted after 440 OS events had been observed.
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) From Date of First Dose until Disease Progression or Death Due to Any Cause (Up To 31 Months) ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites M2 and M20 Cycle 1 Day 1 2-4 hours (h) post dose, Cycle 1 Day 15 4 and 7h post dose, Cycle 2 Day 1 pre dose and 3h post dose, Cycle 3 Day1 pre dose Area Under the Plasma Concentration versus Time Curve from Time Zero to Infinity (AUC\[0-∞\]) was evaluated for Abemaciclib and Metabolites M2 and M20.
Change From Baseline to Short Term Follow up in Quality of Life Using the EORTC QLQ-BR23 (Breast) Questionnaire Baseline, Short Term Follow Up (Up To 31 Months) EORTC-QLQ-BR23 measured multi-item functional scales for body image, sexual functioning and future perspective and measured single item symptoms scales which assessed systemic therapy side effects, breast symptoms and arm symptoms. For functional scales, scores ranged from 0 to 100 where higher scores represented a better level of functioning. For symptoms scales, scores ranged from 0 to 100 where higher scores represented a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment\*Visit and baseline.
Change From Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L) Baseline, End of Study (Up To 31 Months) European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) is a standardized measure of health status of the participant. The EQ-5D-5L is assessed using a visual analog scale (VAS) that ranged from 0 to 100mm, where 0 is the worst health you can imagine and 100 is the best health you can imagine. A higher score indicates better health state. LS Mean value was controlled for Treatment, visit, Treatment\*Visit and baseline.
Change From Baseline to Short Term Follow up in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Baseline, Short Term Follow Up (Up To 31 Months) EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, scores range from 0 to 110 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment\*Visit and baseline.
Trial Locations
- Locations (139)
OCA Hospital
🇲🇽Monterrey, Nuevo León, Mexico
Kaiser Permanente
🇺🇸Riverside, California, United States
University of California - San Diego
🇺🇸La Jolla, California, United States
Stanford University Clinic
🇺🇸Stanford, California, United States
Palm Beach Cancer Institue
🇺🇸West Palm Beach, Florida, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Florida Cancer Specialists - South
🇺🇸Fort Myers, Florida, United States
Florida Cancer Specialists - North
🇺🇸Saint Petersburg, Florida, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Harbin Clinic
🇺🇸Rome, Georgia, United States
Quincy Medical Group
🇺🇸Quincy, Illinois, United States
Pharmasite Research, Inc.
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Washington University Medical School
🇺🇸Saint Peters, Missouri, United States
Freeman Cancer Institute
🇺🇸Joplin, Missouri, United States
Billings Clinic
🇺🇸Billings, Montana, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Rochester General Hospital
🇺🇸Rochester, New York, United States
Oklahoma Cancer Specialists & Research Institute, LLC
🇺🇸Tulsa, Oklahoma, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Oncology Consultants P.A.
🇺🇸Houston, Texas, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
Icon Cancer Centre South Brisbane
🇦🇺South Brisbane, Queensland, Australia
St Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Gold Coast University Hospital
🇦🇺Southport, Queensland, Australia
Ashford Cancer Centre Research
🇦🇺Kurralta Park, South Australia, Australia
Antwerp University Hospital
🇧🇪Edegem, Antwerpen, Belgium
UZ Brussel
🇧🇪Brussel, Bruxelles-Capitale, Région De, Belgium
Tom Baker Cancer Center
🇨🇦Calgary, Alberta, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Humber River Hospital
🇨🇦Toronto, Ontario, Canada
Unity Health Toronto, St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Aalborg Universitets hospital
🇩🇰Aalborg, Denmark
Turun Yliopistollinen Keskussairaala
🇫🇮Turku, Finland
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Pirkanmaa, Finland
CHU Besançon
🇫🇷Besancon, Doubs, France
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
🇫🇷Clermont-Ferrand, Puy-de-Dôme, France
Polyclinique De Blois
🇫🇷La Chaussee Saint Victor, France
Clinique Victor Hugo - Centre Jean Bernard
🇫🇷Le Mans, France
Klinikum Ludwigsburg
🇩🇪Ludwigsburg, Baden-Württemberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Gemeinschaftspraxis hop-augsburg
🇩🇪Augsburg, Bayern, Germany
Klinikum der Ludwig-Maximilians-Universitaet Muenchen
🇩🇪München, Bayern, Germany
Facharztzentrum Eppendorf
🇩🇪Hamburg, Germany
University Hospital of Patras
🇬🇷Patras, Achaḯa, Greece
Agios Savvas Regional Cancer Hospital
🇬🇷Athens, Attikí, Greece
University General Hospital of Heraklion
🇬🇷Heraklion, Krítí, Greece
Aichi Cancer Center Hospital
🇯🇵Nagoya, Aichi, Japan
Chiba cancer center
🇯🇵Chiba-shi, Chiba, Japan
Kurume General Hospital
🇯🇵Kurume, Fukuoka, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo, Hokkaido, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Niigata, Japan
Saitama Prefectural Cancer Center
🇯🇵Ina-machi, Saitama, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
National Hospital Organization Osaka Medical Center
🇯🇵Osaka, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-do [Chungbuk], Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Namdong-gu, Incheon-gwangyeoksi [Incheon], Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Kyǒnggi-do, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Hospital Angeles
🇲🇽Tijuana, Baja California, Mexico
Ulsan University Hospital
🇰🇷Ulsan, Ulsan-Kwangyǒkshi, Korea, Republic of
Instituto Nacional de Cancerologia
🇲🇽Mexico City, Distrito Federal, Mexico
Preparaciones Oncológicas S.C.
🇲🇽Leon, Guanajuato, Mexico
Grupo Medico Camino Sc
🇲🇽Mexico City, Distrito Federal, Mexico
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Pomorskie, Poland
Tecnologico de Monterrey
🇲🇽Monterrey, Nuevo León, Mexico
Centrum Terapii Wspolczesnej J. M. Jasnorzewska Spolka Komandytowo-Akcyjna
🇵🇱Lodz, Łódzkie, Poland
Puerto Rico Hematology/Oncology Group
🇵🇷Bayamon, Puerto Rico
S.C. MedisProf SRL
🇷🇴Cluj-Napoca, Cluj, Romania
Centrul de Oncologie "Sfântul Nectarie"
🇷🇴Craiova, Dolj, Romania
Ianuli Med Consult SRL
🇷🇴Bucharest, Romania
Arkhangelsk Clinical Oncological Dispensary
🇷🇺Arkhangelsk, Arkhangel'skaya Oblast', Russian Federation
Regional Budgetary Healthcare Institution 'Ivanovo Regional Oncology Dispensary'
🇷🇺Ivanovo, Ivanovskaya Oblast', Russian Federation
Fed State Budgetary Inst "N.N. Blokhin Med Center of Oncology" MHRF
🇷🇺Moscow, Moskva, Russian Federation
N.N.Petrov Research Institute of Oncology
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Kursk Regional Oncology Dispensary
🇷🇺Kursk, Russian Federation
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Hospital Universitario Arnau de Vilanova de Lleida
🇪🇸Lleida, Lleida [Lérida], Spain
Hospital General Universitario Morales Meseguer
🇪🇸Murcia, Murcia, Región De, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid, Comunidad De, Spain
Hospital Quirónsalud Valencia
🇪🇸Valencia, València, Spain
Spital Thun
🇨🇭Thun, Berne, Switzerland
HUG-Hôpitaux Universitaires de Genève
🇨🇭Genève, Switzerland
Chang Gung Memorial Hospital at Kaohsiung
🇨🇳Kaohsiung Niao Sung Dist, Kaohsiung, Taiwan
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chang Gung Medical Foundation-Linkou Branch
🇨🇳Taoyuan, Taiwan
Univ of California San Francisco
🇺🇸San Francisco, California, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Minnesota Oncology/Hematology PA
🇺🇸Minneapolis, Minnesota, United States
St. John of God Subiaco Hospital
🇦🇺Subiaco, Western Australia, Australia
St. Bernards Medical Center
🇺🇸Jonesboro, Arkansas, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Chania General Hospital 'Agios Georgios'
🇬🇷Chania, Greece
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Kaohsiung Veterans General Hospital
🇨🇳Kaohsiung, Taiwan
UZ Leuven
🇧🇪Leuven, Vlaams-Brabant, Belgium
Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman
🇧🇪Liège, Belgium
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Jichi Medical University Hospital
🇯🇵Shimotsuke, Tochigi, Japan
Sagara Hospital
🇯🇵Kagoshima, Japan
Saint-Petersburg City Clinical Oncology Dispensary
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
Breslin Cancer Center
🇺🇸Lansing, Michigan, United States
Hyogo College of Medicine
🇯🇵Nishinomiya, Hyogo, Japan
Tokyo Met Cancer & Infectious Diseases Center Komagome Hp
🇯🇵Bunkyo-ku, Tokyo, Japan
The Boston Baskin Cancer Group
🇺🇸Memphis, Tennessee, United States
Japanese Foundation for Cancer Research
🇯🇵Koto, Tokyo, Japan
SMO Sarah Cannon Research Inst.
🇺🇸Nashville, Tennessee, United States
Bialostockie Centrum Onkologii, Oddzial Onkologii Klinicznej
🇵🇱Bialystok, Poland
Sanford Research/USD
🇺🇸Sioux Falls, South Dakota, United States
Centro Oncológico Internacional (COI)
🇲🇽Guadalajara, Jalisco, Mexico
Monash Cancer Centre
🇦🇺East Bentleigh, Victoria, Australia
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Universitätsspital Basel
🇨🇭Basel, Basel Stadt, Switzerland
Helsinki University Hospital - Comprehensive Cancer Center (HYKS - Syöpäkeskus)
🇫🇮Helsinki, Uusimaa, Finland
Azienda Ospedaliero Universitaria S.Anna
🇮🇹Cona, Emilia-Romagna, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Rome, Roma, Italy
Ospedale Bellaria - Azienda USL di Bologna
🇮🇹Bologna, Italy
Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Herlev and Gentofte Hospital
🇩🇰Copenhagen, Hovedstaden, Denmark
Roskilde Sygehus
🇩🇰Roskilde, Denmark
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
The Catholic Univ. of Korea Seoul St. Mary's Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of
Moffitt Cancer Center, Richard M. Shulze Family Foundation Outpatient Center
🇺🇸Tampa, Florida, United States
Novant Health, Oncology Research Institute
🇺🇸Winston-Salem, North Carolina, United States
St Lukes Hospital
🇺🇸Kansas City, Missouri, United States