A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer

Breast Cancer Clinical Trial

— MONARCH plus  

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare NSAI (Anastrozole or Letrozole) Plus Abemaciclib, a CDK4 and CDK6 Inhibitor, or Plus Placebo, and to Compare Fulvestrant Plus Abemaciclib or Plus Placebo in Postmenopausal Women With Hormone Receptor-Positive, HER2-Negative Locoregionally Recurrent or Metastatic Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02763566
• Other study ID #: 15530
• Secondary ID: I3Y-CR-JPBQ
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 5, 2016
• Est. completion date: December 31, 2024

Study information

• Verified date: April 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 efficacy of the study drug abemaciclib in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locoregionally recurrent or metastatic breast cancer.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 463
• Est. completion date: December 31, 2024
• Est. primary completion date: March 29, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have a diagnosis of HR+, HER2- breast cancer. Although not required as a protocol procedure, metastatic disease should be considered for biopsy whenever possible to reassess hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status if clinically indicated.
• To fulfill the requirement for HR+ disease, a breast cancer must express, by immunohistochemistry (IHC), at least 1 of the HRs (estrogen receptor [ER], progesterone receptor [PgR]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• To fulfill the requirement of HER2- disease, a breast cancer must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression of HER2 by either IHC or in-situ hybridization as defined in the relevant ASCO/CAP guidelines.
• Meet either Inclusion Criterion (2a) or Inclusion Criterion (2b). Participants meeting Inclusion Criterion 2a will be enrolled in Cohort A and participants meeting Inclusion Criterion 2b will be enrolled in Cohort B.
• (2a) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease.
• Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease (Note: prior adjuvant endocrine therapy for localized disease may have included, but is not limited to, anti-estrogens or aromatase inhibitors. In addition, a participant may be enrolled if she has received =2 weeks of NSAI in this disease setting immediately preceding screening and agrees to discontinue NSAI until study treatment initiation.) OR
• Presented with de novo metastatic breast cancer (mBC) and not received any prior endocrine therapy. OR
• Relapsed with radiologic evidence of progression less than 1 year from completion of or while receiving adjuvant endocrine therapy (except for letrozole or anastrozole) and have received no prior endocrine therapy for locoregionally recurrent or metastatic disease.
• (2b) Have locoregionally recurrent disease not amenable to resection or radiation therapy with curative intent or metastatic disease.
• Relapsed with radiologic evidence of progression while receiving neoadjuvant or adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR
• Relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy, with no subsequent endocrine therapy received following progression OR
• Relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as firstline endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease OR
• Presented with de novo metastatic disease and then relapsed with radiologic evidence of progression after receiving treatment with either an antiestrogen or an aromatase inhibitor as first-line endocrine therapy for metastatic disease. Participants may not have received more than 1 line of endocrine therapy or any prior chemotherapy for metastatic disease.
• Have postmenopausal status defined as meeting at least 1 of the following:
• Prior bilateral oophorectomy
• Age =60 years
• Age <60 years and amenorrheic for at least 12 months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and follicle-stimulating hormone (FSH) and estradiol levels in the postmenopausal range.
• Have 1 of the following, as defined by the Response Evaluation Criteria in Solid

Tumors (RECIST) v1.1:

• Measurable disease
• Nonmeasurable bone-only disease. Nonmeasurable bone-only disease may include any of the following: blastic bone lesions, lytic bone lesions without a measurable soft tissue component, or mixed lytic-blastic bone lesions without a measurable soft tissue component.
• Have a performance status (PS) of =1 on the Eastern Cooperative Oncology (ECOG) scale.
• Have adequate organ function, including:
• Hematologic: absolute neutrophil count (ANC) =1.5 × 109/Liter (L), platelets =100 × 109/L, and hemoglobin =8 g/deciliter (dL). Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day after the erythrocyte transfusion.
• Hepatic: Total bilirubin =1.5 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3.0 times ULN (or ALT and AST =5 times ULN if liver metastases are present).
• Renal: serum creatinine =1.5 times ULN.
• Have discontinued previous localized radiotherapy for palliative purposes or for lytic lesions at risk of fracture at least 2 weeks prior to randomization 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.
• Are able to swallow capsules.
• Are reliable, willing to be available for the duration of the study, and willing to follow study procedures.

Exclusion Criteria:

• Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. Visceral crisis is not the mere presence of visceral metastases, but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
• Have inflammatory breast cancer.
• Have clinical evidence or a history of central nervous system (CNS) metastasis. Screening test is not required for enrollment.
• Are currently receiving or have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer. (Note: Participants may be enrolled if they received prior [neo]adjuvant chemotherapy for localized disease.)
• Have received prior treatment with everolimus or fulvestrant (for Cohort B only).
• Have received prior treatment with any cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) inhibitor (or participated in any CDK4 and CDK6 inhibitor clinical trial for which treatment assignment is still blinded).
• Have initiated bisphosphonates or approved Receptor activator of nuclear factor kappa-B ligand (RANK-L) targeted agents <7 days prior to randomization.
• Are currently enrolled in a clinical trial involving an investigational product (IP) or non-approved use of a drug or device (other than the IP/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. If a participant is currently enrolled in a clinical trial involving non-approved use of a device, then agreement with the investigator and Eli Lilly and Company (Lilly) clinical research physician (CRP) is required to establish eligibility.
• Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days of randomization for a nonmyelosuppressive or myelosuppressive agent, respectively.
• Have had major surgery within 14 days prior to randomization to allow for post-operative healing of the surgical wound and site(s).
• Have received recent (within 28 days prior to randomization) live attenuated vaccines such as yellow fever vaccine.
• Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (eg, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis).
• Have a personal history within the last 12 months of any of the following conditions:

syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.

• Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years.
• Have received an autologous or allogeneic stem-cell transplant.
• Have clinical evidence of active bacterial or fungal infection or active viral infection that, in the judgment of the investigator, would preclude participation in this study (eg, human immunodeficiency virus [HIV] or viral hepatitis). Screening test is not required for enrollment.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Abemaciclib
Administered orally
• Anastrozole
Administered orally
• Letrozole
Administered orally
• Placebo
Administered orally
• Fulvestrant
Administered intramuscularly

Locations

Country	Name	City	State
Brazil	Fundação Pio XII - F44tal de Câncer de Barretos	Barretos	Sao Paulo
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia	Ijui	Rio Grande Do Sul
Brazil	Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital de Base de Sao Jose do Rio Preto	São José do Rio Preto	Sao Paulo
Brazil	Icesp - Instituto Do Câncer Do Estado de São Paulo	Sao Paulo
Brazil	Clínica de Pesquisa e Centro de Estudos em Ginecologia Oncológica e Mamária LTDA	São Paulo
China	Beijing Cancer Hospital	Beijing	Beijing
China	The Fifth Medical Center of PLA General Hospital	Beijing	Beijing
China	Afflilated Hospital of Bengbu Medical College	Bengbu	Anhui
China	Jilin Cancer Hospital	Chang Chun	Ji Lin
China	Hunan Cancer Hospital	Changsha	Hunan
China	The 2nd Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Provincial Cancer hospital	Fuzhou	Fujian
China	Fuzhou General hospital of Nanjing Military Command	Fuzhou	Fujian
China	Guangdong Province People's Hospital	Guangzhou	Guangdong
China	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University	Guangzhou	Guangdong
China	The Second Affiliate Hospital of Zhejiang University School of medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Caner Hospital	Harbin	Heilongjiang
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guang XI
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	Shanghai General Hospital	Shanghai	Shanghai
China	Liaoning Cander Hospital&Institute	Shenyang	Liaoning
China	The first affiliated hospital of China medical university	Shenyang	Liaoning
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospital	Wuhan	Hubei
China	Tongji Hospital Tongji Medical, Science & Technology	Wuhan	Hubei
China	Wuhan Union Hospital Cancer Center	Wuhan	Hubei
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	Henan Cancer Hospital	Zhengzhou	Henan
India	The Gujarat Cancer & Research Institute (GCRI)	Ahmedabad	Gujarat
India	Healthcare Global Enterprises Limited (HCG)	Bangalore	Karnataka
India	M S Ramaiah Medical College Hospitals	Bangalore	Karnataka
India	Medica Superspecialty Hospital	Kolkata	West Bengal
India	Tata Memorial Hospital	Mumbai	Maharashtra
India	Dr. B. L. Kapur Memorial Hospital	New Delhi	Delhi
India	Jehangir Hospital	Pune	Maharashtra
India	Christian Medical College Vellore	Ranipet	Tamil Nadu
South Africa	Sandton Oncology Centre	Johannesburg
South Africa	The Medical Oncology Centre of Rosebank	Johannesburg	Gauteng
South Africa	Eastleigh Breast Care Center	Pretoria	Gauteng

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Brazil,  China,  India,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) (Abemaciclib + NSAI & Placebo NSAI)	Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. 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. Patients 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.	Randomization to Measured Progressive Disease or Death (up to 26 Months)
Secondary	Progression Free Survival (PFS) (Abemaciclib + Fulvestrant and Placebo + Fulvestrant Arms)	Progression-free survival time was measured from randomization until the date of objective progression as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), or death from any cause. 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. Patients 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.	Randomization to Measured Progressive Disease or Death (up to 26 Months)
Secondary	Overall Survival (OS)		Randomization to Date of Death from Any Cause (Estimated up to 38 Months)
Secondary	Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]	Objective response rate is the percentage of participants with a BOR of CR or PR as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is 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.	Randomization to Measured Progressive Disease (up to 26 Months)
Secondary	Duration of Response (DoR)		Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 38 Months)
Secondary	Percentage of Participants Who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)]	Disease control rate (DCR) is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. 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.	Randomization to Measured Progressive Disease (up to 26 Months)
Secondary	Percentage of Participants With Best Overall Response of CR, PR, or SD With Duration of SD for at Least 6 Months [Clinical Benefit Rate (CBR)]	Clinical benefit rate (CBR) is the percentage of participants with a BOR of CR or PR, or SD for at least 6 months. CR is defined as the disappearance of all target and non-target lesions & no appearance of new lesions. PR is 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 is 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 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.	Randomization to Measured Progressive Disease (up to 26 Months)
Secondary	Change From Randomization in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)	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 through 19 Months
Secondary	Pharmacokinetics (PK): Area Under the Concentration Curve of Abemaciclib, Its Metabolites (M2 & M20)	Pharmacokinetics (PK): Area Under the Concentration Curve of Abemaciclib and its Metabolites LSN2839567 (M2) & LSN3106726 (M20) was reported.; C=Cycle, D=day;	C1D1 post dose, C2D1 post dose, C3D1 predose, C4D1 predose

External Links

•   A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer