Metastatic Breast CancerPhase 2Next MONARCH 1NCT02747004
A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer
A Phase 2 study testing Abemaciclib, Tamoxifen and Prophylactic Loperamide in people with Metastatic Breast Cancer, run by Eli Lilly and Company at 59 sites in 14 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Abemaciclib, Tamoxifen and Prophylactic Loperamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 234 participants
- Where
- 59 sitesin 14 countries
- Study dates
- 14 Sep 2016to 9 Sep 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
59 sites in 14 countries.
59 sites in 14 countries
Spain7 sites
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [Barcelona], 08035
Hospital Clinic I Provincial
Barcelona, 08036
Hospital Universitario Ramón y Cajal
Madrid, Madrid, Comunidad de, 28034
Hospital General Universitario Gregorio Marañon
Madrid, 28007
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Clínico Universitario de Valencia
Valencia, 46010
Argentina6 sites
CENIT Centro de Neurociencias, Investigación y Tratamiento
CABA, Buenos Aires, C1125ABD
Instituto de Oncología de Rosario
Rosario, Santa Fe Province, S2000KZE
Sanatorio Parque
Salta, 4400
Centro Para la Atención Integral del Paciente Oncologico (CAIPO)
San Miguel de Tucumán, Tucumán Province, 4000
Fundacion Ars Medica
San Salvador de Jujuy, Jujuy Province, Y4600APW
Clinica Viedma
Viedma, Río Negro Province, R8500ACE
United States5 sites
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03766
University of Wisconsin Clinical Research Center
Madison, Wisconsin, 53705
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
The University of Arizona Cancer Center
Tucson, Arizona, 85724
Czechia5 sites
Masarykuv onkologicky ustav
Brno, Czech Republic, 656 53
Fakultni nemocnice Kralovske Vinohrady
Prague, 100 34
Fakultni Poliklinika VFN
Prague, 128 08
Fakultni Nemocnice v Motole
Prague, 150 06
Thomayerova nemocnice
Praha 4 - Krc, 140 59
Taiwan5 sites
Taipei Medical University Shuang Ho Hospital
New Taipei City, 235
China Medical University Hospital
Taichung, 40447
Mackay Memorial Hospital
Taipei, 10449
Taipei Veterans General Hospital
Taipei, 11217
Chang Gung Memorial Hospital - Linkou
Taoyuan City, 33305
Turkey (Türkiye)5 sites
Baskent University Dr. Turgut Noyan Research and Training Center
Adana, 1250
Hacettepe University Faculty of Medicine
Ankara, 06100
Medipol Mega University Hospital
Istanbul, Turkey, 34214
Marmara University Medical Faculty
Istanbul, 34668
Erciyes University Faculty of Medicine
Kayseri, Melikgazi, 38039
Belgium4 sites
Grand Hopital de Charleroi-Site Notre-Dame
Charleroi, 6000
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, 9000
Centre Hospitalier Universitaire Sart Tilman
Liège, 4000
VITAZ
Sint-Niklaas, Oost-Vlaanderen, 9100
Brazil4 sites
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, 14784400
Hospital São Lucas - PUCRS - ONCOLOGY
Porto Alegre, Rio Grande do Sul, 90610-000
Icesp - Instituto Do Câncer Do Estado de São Paulo
São Paulo, 01246000
Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA
São Paulo, 01317-000
Italy4 sites
Ospedale Bellaria - Azienda USL di Bologna
Bologna, 40139
Azienda Ospedaliera Universitaria Federico II
Naples, 80131
Ospedale Sacro Cuore Don G. Calabria
Negrar, Verona, 37024
Polic.Umberto I -Univ. La Sapienza
Roma, Rome, 00161
Mexico4 sites
Neurociencias Estudios Clinicos
Culiacán, Sinaloa, 80020
Grupo Medico Camino Sc
Mexico City, 03310
Oaxaca Site Management Organization
Oaxaca City, 68000
Centro Hemato Oncologico Privado
San Bernardino, Toluca, 50080
Austria3 sites
Medizinische Universitaet Graz
Graz, Styria, 8036
Universitätsklinik Innsbruck
Innsbruck, Tyrol, 6020
AKH
Vienna, 1090
Russia3 sites
Republic Oncology Dispensary of MoH of Republic Tatarstan
Kazan', 420029
St-Petersburg scientifical practical center of specialized medical care
Saint Petersburg, 197758
Saint-Petersburg city clinical oncology dispensary
Saint Petersburg, 198255
France2 sites
Centre Oscar Lambret
Lille, Hauts-de-France, 59020
Institut Paoli-Calmettes
Marseille, Provence-Alpes-Côte d'Azur Region, 13273
Germany2 sites
Kath. Marienkrankenhaus gGmbH
Hamburg, 22087
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
About this study
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
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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Abemaciclib, Tamoxifen, Prophylactic Loperamide
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called LY2835219
Administered orally
TamoxifenDrug
Administered orally
Prophylactic LoperamideDrug
Administered orally
| Study group | Role | What they receive |
|---|---|---|
| Abemaciclib + Tamoxifen | Experimental | Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met. Receives: Drug: Abemaciclib; Drug: Tamoxifen |
| Abemaciclib | Experimental | Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met. Receives: Drug: Abemaciclib |
| Abemaciclib + Prophylactic Loperamide | Experimental | Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met. Receives: Drug: Abemaciclib; Drug: Prophylactic Loperamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Progression-free survival time was measured from the date of randomization to the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as 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. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.
Measured: Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)
Secondary outcomes (9)
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
Objective response rate was defined as the percentage of participants with CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD (longest diameter) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
Measured: Baseline to Objective Disease Progression (Up to 21 Months)
Duration of Response (DoR)
DoR is defined as the time from the date of first evidence of a CR or PR to the date of objective progression or death from any cause, whichever is earlier as defined by Recist v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was 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.
Measured: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months)
Overall Survival (OS)
Measured: Baseline to Death from Any Cause (Approximately 36 Months)
Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites
Mean single dose concentrations of Abemaciclib and its metabolites (M2 \& M20) are reported.
Measured: Cycle (C) 1 Day (D) 1 post dose
Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and Its Metabolites
Mean steady state concentrations of Abemaciclib and its metabolites (M2 \& M20) are reported.
C=Cycle D= Day
Measured: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen
Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.
Measured: Cycle 1 Day 1 post dose
PK: Multiple Dose Concentration of Tamoxifen and Endoxifen
Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.
Measured: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions:
- Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).
- Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much)
- Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much).
Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden.
Measured: Baseline, 21 Months
Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)
mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes.
Measured: Baseline, 21 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2016 (estimated)
- Study start14 Sep 2016
- Primary completion15 Jun 2018
- Study completion9 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 234 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02747004
- Sponsor's protocol ID
- 16339
- Other IDs
- I3Y-MC-JPCG, 2016-000288-18, 2016
- Acronym
- Next MONARCH 1
- Status last verified
- Sep 2026
- First submitted
- 19 Apr 2016
- Last updated
- 16 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
- Expanded access
- Available
Publications
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.
PubMed 35829935