Clinical trial NCT02747004: A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer
Official title: A Randomized, Open-Label, Phase 2 Study of Abemaciclib Plus Tamoxifen or Abemaciclib Alone, in Women With Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-04-21
Enrollment: 234
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.


Eligibility criteria: Inclusion Criteria:

* Have a diagnosis of HR+, HER2- breast cancer.
* Relapsed or progressed following endocrine therapy.
* Have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but no more than 2 have been administered in the metastatic setting.
* Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
* Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
* Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy.
* Have adequate organ function.
* Have negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective precautions to prevent pregnancy during the study and for 3 weeks following last dose of study treatment.
* Are able to swallow oral medication.

Exclusion Criteria:

* Have clinical evidence or history of central nervous system metastasis.
* Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
* Have active bacterial or fungal infection (that is, requiring intravenous antibiotics at the time of initiating study treatment) and/or detectable viral infection.
* Have received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.
* Have a preexisting chronic condition resulting in persistent diarrhea.
* Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix or breast), unless in complete remission with no therapy for a minimum of 3 years.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)
Secondary outcomes:
measure: Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
timeFrame: Baseline to Objective Disease Progression (Up to 21 Months)
measure: Duration of Response (DoR)
timeFrame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months)
measure: Overall Survival (OS)
timeFrame: Baseline to Death from Any Cause (Approximately 36 Months)
measure: Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites
timeFrame: Cycle (C) 1 Day (D) 1 post dose
measure: Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and Its Metabolites
timeFrame: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
measure: PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen
timeFrame: Cycle 1 Day 1 post dose
measure: PK: Multiple Dose Concentration of Tamoxifen and Endoxifen
timeFrame: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
measure: Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
timeFrame: Baseline, 21 Months
measure: Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
timeFrame: Baseline, 21 Months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Clinical Research Center
state: Wisconsin
city: Caba
country: Argentina
facility: CENIT Centro de Neurociencias, Investigación y Tratamiento
state: Buenos Aires
city: San Salvador de Jujuy
country: Argentina
facility: Fundacion Ars Medica
state: Jujuy
city: Viedma
country: Argentina
facility: Clinica Viedma
state: Río Negro
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
state: Santa Fe
city: San Miguel de Tucuman
country: Argentina
facility: Centro Para la Atención Integral del Paciente Oncologico (CAIPO)
state: Tucumán
city: Salta
country: Argentina
facility: Sanatorio Parque
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Universitätsklinik Innsbruck
state: Tyrol
city: Wien
country: Austria
facility: AKH
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
state: Oost-Vlaanderen
city: Sint-Niklaas
country: Belgium
facility: VITAZ
state: Oost-Vlaanderen
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi-Site Notre-Dame
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire Sart Tilman
city: Porto Alegre
country: Brazil
facility: Hospital São Lucas - PUCRS - ONCOLOGY
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Icesp - Instituto Do Câncer Do Estado de São Paulo
city: São Paulo
country: Brazil
facility: Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
state: Czech Republic
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha 2
country: Czechia
facility: Fakultni Poliklinika VFN
city: Praha 4 - Krc
country: Czechia
facility: Thomayerova nemocnice
city: Praha 5
country: Czechia
facility: Fakultni Nemocnice v Motole
city: Lille
country: France
facility: Centre Oscar Lambret
state: Nord-Pas-de-Calais
city: Marseille
country: France
facility: Institut Paoli-Calmettes
state: Provence-Alpes-Côte-d'Azur
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Hamburg
country: Germany
facility: Kath. Marienkrankenhaus gGmbH
city: Roma
country: Italy
facility: Polic.Umberto I -Univ. La Sapienza
state: Rome
city: Negrar Di Valpolicella
country: Italy
facility: Ospedale Sacro Cuore Don G. Calabria
state: Verona
city: Bologna
country: Italy
facility: Ospedale Bellaria - Azienda USL di Bologna
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Culiacan
country: Mexico
facility: Neurociencias Estudios Clinicos
state: Sinaloa
city: San Bernardino
country: Mexico
facility: Centro Hemato Oncologico Privado
state: Toluca
city: Mexico City
country: Mexico
facility: Grupo Medico Camino Sc
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization
city: Kazan
country: Russian Federation
facility: Republic Oncology Dispensary of MoH of Republic Tatarstan
city: Saint Petersburg
country: Russian Federation
facility: St-Petersburg scientifical practical center of specialized medical care
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg city clinical oncology dispensary
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
state: Madrid, Comunidad De
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: New Taipei
country: Taiwan
facility: Taipei Medical University Shuang Ho Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Kayseri
country: Turkey
facility: Erciyes University Faculty of Medicine
state: Melikgazi
city: Adana
country: Turkey
facility: Baskent University Dr. Turgut Noyan Research and Training Center
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Istanbul
country: Turkey
facility: Medipol Mega University Hospital
city: Istanbul
country: Turkey
facility: Marmara University Medical Faculty
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Hamilton E, Cortes J, Ozyilkan O, Chen SC, Petrakova K, Manikhas A, Jerusalem G, Hegg R, Huober J, Zhang W, Chen Y, Martin M. nextMONARCH Phase 2 randomized clinical trial: overall survival analysis of abemaciclib monotherapy or in combination with tamoxifen in patients with endocrine-refractory HR + , HER2- metastatic breast cancer. Breast Cancer Res Treat. 2022 Aug;195(1):55-64. doi: 10.1007/s10549-022-06662-9. Epub 2022 Jul 12.