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

ID: NCT02763566
Status: Recruiting
Phase: Phase 3
Start Date: December 01, 2016
First Submitted: May 04, 2016
Last Updated: February 14, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company
Location: Brazil, China, India, South Africa
Conditions: Breast Cancer
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Study Description

Brief 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.

Detailed Description

Condition or disease Intervention/treatment Phase

Breast Cancer

Drug: Abemaciclib
Other Names
LY2835219
Drug: Anastrozole
Other Names
Drug: Letrozole
Other Names
Drug: Placebo
Other Names
Drug: Fulvestrant
Other Names
Phase 3

Tracking Information

First Submitted DateMay 04, 2016
Last Update Posted DateFebruary 14, 2018
Start DateDecember 01, 2016
Anticipated Completion DateJanuary 01, 2020
Primary Completion DateJanuary 01, 2020
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Progression Free Survival (PFS) [Time Frame: Randomization to Measured Progressive Disease or Death (Estimated up to 38 Months)]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Overall Survival (OS) [Time Frame: Randomization to Date of Death from Any Cause (Estimated up to 38 Months)]

  • Proportion of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)] [Time Frame: Randomization to Measured Progressive Disease (Estimated up to 38 Months)]

  • Duration of Response (DoR) [Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 38 Months)]

  • Proportion of Participants who Exhibit Stable Disease (SD) or CR or PR [Disease Control Rate (DCR)] [Time Frame: Randomization to Measured Progressive Disease (Estimated up to 38 Months)]

  • Proportion of Participants with Best Overall Response of CR, PR, or SD with Duration of SD for at Least 6 Months [Clinical Benefit Rate (CBR)] [Time Frame: Randomization to Measured Progressive Disease (Estimated up to 38 Months)]

  • Change from Randomization in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [Time Frame: Randomization, Follow-Up (Estimated up to 38 Months)]

  • Pharmacokinetics (PK): Area Under the Concentration Curve of Abemaciclib, its Metabolites, NSAI, and Fulvestrant [Time Frame: Post Dose Cycle 1 Day 1 through Pre-Dose Cycle 4 Day 1 (28 day cycles)]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Abemaciclib (LY2835219) in Participants With Breast Cancer
Official TitleA 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
Brief 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.

Detailed Description

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
450
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Double
Primary Purpose
Treatment
Conditions
Breast Cancer
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Abemaciclib

Administered orally

Other Names
LY2835219
Drug: Anastrozole

Administered orally

Other Names
Drug: Letrozole

Administered orally

Other Names
Drug: Placebo

Administered orally

Other Names
Drug: Fulvestrant

Administered intramuscularly

Other Names
Study Groups/Cohorts
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.

Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.

Abemaciclib + Fulvestrant
Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.

Placebo + Fulvestrant
Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.

Study Arms
Experimental Abemaciclib + Fulvestrant
Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Fulvestrant
Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Fulvestrant
Administered intramuscularly

Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Abemaciclib
Administered orally

Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Anastrozole
Administered orally

Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Letrozole
Administered orally

Experimental Placebo + Fulvestrant
Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Placebo
Administered orally

Experimental Placebo + Fulvestrant
Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Fulvestrant
Administered intramuscularly

Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Letrozole
Administered orally

Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Placebo
Administered orally

Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Anastrozole
Administered orally

Arm Intervention/Treatment
Experimental Abemaciclib + Fulvestrant
Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Abemaciclib
Experimental Abemaciclib + Fulvestrant
Abemaciclib given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Fulvestrant
Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Abemaciclib
Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Anastrozole
Experimental Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
Abemaciclib given orally every 12 hours (Q12H) plus anastrozole or letrozole given orally every 24 hours (Q24H) on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Letrozole
Experimental Placebo + Fulvestrant
Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Placebo
Experimental Placebo + Fulvestrant
Placebo given orally Q12H on days 1 to 28 of a 28 day cycle plus fulvestrant IM on days 1 and 15 of cycle 1, then on day 1 of cycle 2 and beyond. Participants receiving benefit may continue until disease progression.
Drug : Fulvestrant
Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Letrozole
Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Placebo
Experimental Placebo + NSAI
Placebo given orally Q12H plus anastrozole or letrozole given orally Q24H on days 1 to 28 of a 28 day cycle. Participants receiving benefit may continue until disease progression.
Drug : Anastrozole

Recruitment Information

Recruitment Status:Recruiting
Enrollment450
Completion DateJanuary 01, 2020
Eligibility Criteria: 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 de novo metastatic breast cancer (mBC) and not received any prior endocrine therapy.
- (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 de novo with 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.
GenderFemale
Age18 Years to N/A
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Brazil
China
India
South Africa

Administrative Information

NCT Number:NCT02763566
Other Study ID Numbers
15530
I3Y-CR-JPBQ
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
Not Available
Investigators
Study Director
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)
Eli Lilly and Company