A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer

Metastatic Breast Cancer Clinical Trial

— Next MONARCH 1  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02747004
• Other study ID #: 16339
• Secondary ID: I3Y-MC-JPCG2016-
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 14, 2016
• Est. completion date: December 30, 2024

Study information

• Verified date: June 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 234
• Est. completion date: December 30, 2024
• Est. primary completion date: June 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Abemaciclib
Administered orally
• Tamoxifen
Administered orally
• Prophylactic Loperamide
Administered orally

Locations

Country	Name	City	State
Argentina	CENIT Centro de Neurociencias, Investigación y Tratamiento	Caba	Buenos Aires
Argentina	Instituto de Oncología de Rosario	Rosario	Santa Fe
Argentina	Sanatorio Parque	Salta
Argentina	Centro Para la Atención Integral del Paciente Oncologico (CAIPO)	San Miguel de Tucuman	Tucumán
Argentina	Fundacion Ars Medica	San Salvador de Jujuy	Jujuy
Argentina	Clinica Viedma	Viedma	Río Negro
Austria	Medizinische Universitaet Graz	Graz	Steiermark
Austria	Universitätsklinik Innsbruck	Innsbruck	Tyrol
Austria	AKH	Wien
Belgium	Grand Hopital de Charleroi-Site Notre-Dame	Charleroi
Belgium	Universitair Ziekenhuis Gent	Gent	Oost-Vlaanderen
Belgium	Centre Hospitalier Universitaire Sart Tilman	Liege
Belgium	VITAZ	Sint-Niklaas	Oost-Vlaanderen
Brazil	Fundação Pio XII - Hospital de Câncer de Barretos	Barretos	Sao Paulo
Brazil	Hospital São Lucas - PUCRS - ONCOLOGY	Porto Alegre	Rio Grande Do Sul
Brazil	Icesp - Instituto Do Câncer Do Estado de São Paulo	Sao Paulo
Brazil	Clinica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária LTDA	São Paulo
Czechia	Masarykuv onkologicky ustav	Brno	Czech Republic
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 10
Czechia	Fakultni Poliklinika VFN	Praha 2
Czechia	Thomayerova nemocnice	Praha 4 - Krc
Czechia	Fakultni Nemocnice v Motole	Praha 5
France	Centre Oscar Lambret	Lille	Nord-Pas-de-Calais
France	Institut Paoli-Calmettes	Marseille	Provence-Alpes-Côte-d'Azur
Germany	Kath. Marienkrankenhaus gGmbH	Hamburg
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Italy	Ospedale Bellaria - Azienda USL di Bologna	Bologna
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Ospedale Sacro Cuore Don G. Calabria	Negrar Di Valpolicella	Verona
Italy	Polic.Umberto I -Univ. La Sapienza	Roma	Rome
Mexico	Neurociencias Estudios Clinicos	Culiacan	Sinaloa
Mexico	Grupo Medico Camino Sc	Mexico City
Mexico	Oaxaca Site Management Organization	Oaxaca
Mexico	Centro Hemato Oncologico Privado	San Bernardino	Toluca
Russian Federation	Republic Oncology Dispensary of MoH of Republic Tatarstan	Kazan
Russian Federation	Saint-Petersburg city clinical oncology dispensary	Saint Petersburg
Russian Federation	St-Petersburg scientifical practical center of specialized medical care	Saint Petersburg
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid	Madrid, Comunidad De
Spain	Hospital Clínico Universitario de Valencia	Valencia
Taiwan	Taipei Medical University Shuang Ho Hospital	New Taipei
Taiwan	China Medical University Hospital	Taichung
Taiwan	Mackay Memorial Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan City
Turkey	Baskent University Dr. Turgut Noyan Research and Training Center	Adana
Turkey	Hacettepe University Faculty of Medicine	Ankara
Turkey	Marmara University Medical Faculty	Istanbul
Turkey	Medipol Mega University Hospital	Istanbul
Turkey	Erciyes University Faculty of Medicine	Kayseri	Melikgazi
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Wisconsin Clinical Research Center	Madison	Wisconsin
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	The University of Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Belgium,  Brazil,  Czechia,  France,  Germany,  Italy,  Mexico,  Russian Federation,  Spain,  Taiwan,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months)
Secondary	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.	Baseline to Objective Disease Progression (Up to 21 Months)
Secondary	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.	Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months)
Secondary	Overall Survival (OS)		Baseline to Death from Any Cause (Approximately 36 Months)
Secondary	Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites	Mean single dose concentrations of Abemaciclib and its metabolites (M2 & M20) are reported.	Cycle (C) 1 Day (D) 1 post dose
Secondary	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	Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
Secondary	PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen	Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.	Cycle 1 Day 1 post dose
Secondary	PK: Multiple Dose Concentration of Tamoxifen and Endoxifen	Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.	Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose
Secondary	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.	Baseline, 21 Months
Secondary	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.	Baseline, 21 Months

External Links

•   A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer (nextMONARCH 1)