Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer (monarchE)

• ClinicalTrials.gov Identifier: NCT03155997
• Recruitment Status: Active, not recruiting
• First Posted: May 16, 2017
• Last Update Posted: November 20, 2020
• Sponsor: Eli Lilly and Company
• Collaborator: NSABP Foundation Inc
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: May 15, 2017
• First Posted Date: May 16, 2017
• Last Update Posted Date: November 20, 2020
• Actual Study Start Date: July 12, 2017
• Actual Primary Completion Date: March 16, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 13, 2017)

Invasive Disease Free Survival (IDFS) [ Time Frame: Baseline to Recurrence or Death from Any Cause (Approximately 10 Years) ]

IDFS

Original Primary Outcome Measures (submitted: May 15, 2017)

Invasive Disease Free Survival (IDFS) [ Time Frame: Baseline to Recurrence or Death from Any Cause (Approximately 5 Years) ]

IDFS

Current Secondary Outcome Measures (submitted: November 13, 2017)

• IDFS for Participants with Ki-67 Index ≥20% [ Time Frame: Baseline to Recurrence or Death from Any Cause (Approximately 10 Years) ]
  IDFS for participants with Ki-67 index ≥20%
• Distant Relapse-Free Survival (DRFS) [ Time Frame: Baseline to Distant Recurrence or Death from Any Cause (Approximately 10 Years) ]
  DRFS
• Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 10 Years) ]
  OS
• Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib [ Time Frame: Post Dose Day 1 through Month 3 ]
  PK: Cmin,ss of Abemaciclib
• Change from Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACT-B
• Change from Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACT-ES
• Change from Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACIT-F
• Change from Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the EQ-5D-5L

Original Secondary Outcome Measures (submitted: May 15, 2017)

• IDFS for Participants with Ki-67 Index ≥20% [ Time Frame: Baseline to Recurrence or Death from Any Cause (Approximately 5 Years) ]
  IDFS for participants with Ki-67 index ≥20%
• Distant Relapse-Free Survival (DRFS) [ Time Frame: Baseline to Distant Recurrence or Death from Any Cause (Approximately 5 Years) ]
  DRFS
• Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 5 Years) ]
  OS
• Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib [ Time Frame: Post Dose Day 1 through Month 3 ]
  PK: Cmin,ss of Abemaciclib
• Change from Baseline on the Functional Assessment of Cancer Therapy - Breast (FACT-B) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACT-B
• Change from Baseline on the Functional Assessment of Cancer Therapy - Endocrine Symptoms (FACT-ES) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACT-ES
• Change from Baseline on the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the FACIT-F
• Change from Baseline on the EuroQol Five-Dimension Five-Level Questionnaire (EQ-5D-5L) [ Time Frame: Baseline, Follow Up (Approximately 3 Years) ]
  Change from Baseline on the EQ-5D-5L

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Endocrine Therapy With or Without Abemaciclib (LY2835219) Following Surgery in Participants With Breast Cancer
• Official Title: A Randomized, Open-Label, Phase 3 Study of Abemaciclib Combined With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone in Patients With High Risk, Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer
• Brief Summary: The purpose of this study is to evaluate the safety and efficacy of the study drug abemaciclib in participants with high risk, node positive, early stage, hormone receptor positive (HR+), human epidermal receptor 2 negative (HER2-), breast cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• Drug: Abemaciclib
  Administered orally.
  Other Name: LY2835219
• Drug: Standard Adjuvant Endocrine Therapy
  Administered according to label instructions.

Study Arms

• Experimental: Abemaciclib + Standard Adjuvant Endocrine Therapy
  Abemaciclib administered orally and standard adjuvant endocrine therapy administered according to package label.
  Interventions:

  • Drug: Abemaciclib
  • Drug: Standard Adjuvant Endocrine Therapy
• Standard Adjuvant Endocrine Therapy
  Standard adjuvant endocrine therapy administered according to package label.
  Intervention: Drug: Standard Adjuvant Endocrine Therapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 25, 2019): 4580
• Original Estimated Enrollment (submitted: May 15, 2017): 3580
• Estimated Study Completion Date: June 24, 2029
• Actual Primary Completion Date: March 16, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Women (regardless of menopausal status) or men ≥18 years of age (or per local regulations).
• The participant has confirmed HR+, HER2-, early stage resected invasive breast cancer without evidence of distant metastases.
• The participant must have undergone definitive surgery of the primary breast tumor.
• The participant must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization.

• Pathologic lymph node involvement and at least one of the following indicating a higher risk of recurrence:

  • 4 or more positive axillary lymph nodes
  • Tumor size of at least 5 centimeters
  • Grade 3 defined as at least 8 points on the Bloom Richardson grading system
  • Ki-67 index by central analysis of ≥20% on untreated breast tissue
• The participant must be randomized within 16 months from the time of definitive breast cancer surgery.
• The participant may receive up to 12 weeks of endocrine therapy until randomization following the last non-endocrine therapy (surgery, chemotherapy, or radiation) whichever is last.
• Participants must have recovered (grade ≤1) from the acute effects of chemotherapy and radiotherapy and from surgical side effects following definitive breast surgery.
• Women of reproductive potential must have a negative blood pregnancy test and agree to use highly effective contraceptive methods.
• The participant has a Eastern Cooperative Oncology Group (ECOG) performance status ≤1.
• The participant has adequate organ function.
• The participant is able to swallow oral medications.

Exclusion Criteria:

• Metastatic disease (including contralateral axillary lymph nodes) or node-negative disease.
• Participants with inflammatory breast cancer.
• Participants with a history of previous breast cancer, with the exception of ipsilateral ductal carcinoma in situ (DCIS) treated by locoregional therapy alone ≥5 years ago. Participants with a history of contralateral DCIS treated by local regional therapy at any time may be eligible. Participants with a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years from the date of randomization are excluded.
• Females who are pregnant or lactating.
• The participant has previously received treatment with any CDK4 and CDK6 inhibitor.
• The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
• The participant has previously received endocrine therapy for breast cancer prevention (tamoxifen or aromatase inhibitors) or raloxifene.
• The participant has serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
• The participant has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin or sudden cardiac arrest. Any participant with a history of venous thromboembolism (VTE).
• The participant has active systemic infections or viral load.
• The participant has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Romania, Russian Federation, Saudi Arabia, Singapore, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Chile

Administrative Information

• NCT Number: NCT03155997
• Other Study ID Numbers: 16338; I3Y-MC-JPCF ( Other Identifier: Eli Lilly and Company ); 2016-004362-26 ( EudraCT Number ); NSABP B-58 ( Other Identifier: NSABP )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: NSABP Foundation Inc

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

• PRS Account: Eli Lilly and Company
• Verification Date: November 2020