A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Abemaciclib; Anastrozole; Letrozole; Placebo; Fulvestrant
Intervention description: Administered orally; Administered orally; Administered orally; Administered orally; Administered intramuscularly
Intervention MeSH terms: Letrozole; Fulvestrant; Anastrozole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 463.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hormone Receptor-Positive; HER2-Negative; CDK4; CDK6

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.
    

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 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.