Clinical Trials /

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

NCT02763566

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer
  • 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 IDs

  • ORG STUDY ID: 15530
  • SECONDARY ID: I3Y-CR-JPBQ
  • NCT ID: NCT02763566

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
AbemaciclibLY2835219Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
AnastrozoleAbemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
LetrozoleAbemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)
PlaceboPlacebo + NSAI
FulvestrantAbemaciclib + Fulvestrant

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Abemaciclib + Nonsteroidal Aromatase Inhibitor (NSAI)ExperimentalAbemaciclib 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.
  • Abemaciclib
  • Anastrozole
  • Letrozole
Placebo + NSAIExperimentalPlacebo 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.
  • Anastrozole
  • Letrozole
  • Placebo
Abemaciclib + FulvestrantExperimentalAbemaciclib 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.
  • Abemaciclib
  • Fulvestrant
Placebo + FulvestrantExperimentalPlacebo 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.
  • Placebo
  • Fulvestrant

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:Randomization to Measured Progressive Disease or Death (Estimated up to 38 Months)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:Randomization to Date of Death from Any Cause (Estimated up to 38 Months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • Hormone Receptor-Positive
  • HER2-Negative
  • CDK4
  • CDK6

Last Updated

March 8, 2018