Neo-Adjuvant Abemaciclib With Fulvestrant in Patients With ER/PR +HER Negative Breast Cancer
Condition: Breast Neoplasm; Hormone Receptor Positive Breast Carcinoma
MeSH terms: Breast Neoplasms
Intervention: Abemaciclib; Fulvestrant
Intervention description: Given PO; Given Intramuscularly
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 2 single-arm, open-label determining efficacy of Neo-adjuvant Abemaciclib and
      Fulvestrant in subjects with Hormone receptor positive patients with localized non-metastatic
      breast cancer who develop local recurrence while on adjuvant endocrine therapy with molecular
      evidence of endocrine resistance.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have a diagnosis of HR+ breast cancer. To fulfill the requirement of HR+
             disease, a breast cancer must express, by immunohistochemistry (IHC), at least one of
             the hormone receptors (ER, progesterone receptor [PgR]) as defined in the relevant
             American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP)
             Guidelines (Hammond et al. 2010):

             1. For ER and PgR assays to be considered positive, ≥1% of tumor cell nuclei must be
             immunoreactive by immunohistochemistry (IHC) (Hammond et al. 2010).

          -  Patients must have Loco regional breast cancer (Stage I, Stage II and stage III per
             AJCC 8th edition criteria for staging of breast cancer)

          -  Patients must have localized recurrence while on adjuvant endocrine therapy

          -  Patients must have any known molecular evidence of endocrine resistance by next
             generation sequencing

          -  Age ≥ 18 years.

          -  ECOG performance status 0-1

          -  Have post-menopausal status as defined by following:

               1. Prior bilateral oophorectomy

               2. Age ≥ 60 years

               3. Age < 60 and amenorrheic (non-treatment-induced amenorrhea secondary to
                  tamoxifen, toremifene, ovarian suppression, or chemotherapy) for at least 12
                  months. Follicle-stimulating hormone (FSH) and estradiol must be in the
                  postmenopausal range.

          -  Have at least one measurable disease as defined per RECIST 1.1

          -  Adequate organ and marrow function as defined below:

               1. Hemoglobin* > 8 g/dL

               2. Absolute neutrophil count ≥ 1,500/mcL

               3. Total bilirubin ≤ 1.5 X institutional ULN, Patients with Gilbert's syndrome with
                  a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are
                  permitted

               4. AST (SGOT)/ALT (SPGT) ≤ 2.5 X institutional ULN

               5. Creatinine ≤ 1.5 X institutional ULN

                    1. *Patients may receive transfusion of packed red blood cells (PRBC) 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 PRBC transfusion.

          -  Able to swallow oral medications

          -  Patients who received adjuvant radiotherapy must have completed and fully recovered
             from the acute effects of radiotherapy. A washout period of at least 14 days is
             required between end of radiotherapy and screening for the study.

          -  Patients who received chemotherapy must have recovered (Common Terminology Criteria
             for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for
             residual alopecia or Grade 2 peripheral neuropathy prior to enrollment. A washout
             period of at least 21 days is required between last chemotherapy dose and enrollment
             (provided the patient did not receive radiotherapy).

          -  Any known markers of response or resistance to CDK 4/6 inhibitors to be present in the
             biopsy specimen

          -  If patients have been treated with prior Neo-Adjuvant chemotherapy at the time of
             primary diagnosis and not at the time of recurrence, they will be included in the
             study.

          -  Must be able to sign a written informed consent, are reliable, willing to be available
             for the duration of the study and are willing to follow study procedures

        Exclusion Criteria:

          -  Stage IV metastatic breast cancer

             1. This study will utilize the American Joint Committee on Cancer (AJCC) staging
             system, eight edition that provides a strategy for grouping patients with respect to
             prognosis. The AJCC has designated staging by TNM classification. The researchers will
             also review tumor size, lymph node status, and estrogen-receptor and
             progesterone-receptor levels in the tumor tissue.

          -  Patients with HER2 positive and triple negative breast cancer

             1. To fulfill the requirement of HER2- and Triple negative disease, a breast cancer
             must not demonstrate, at initial diagnosis or upon subsequent biopsy, overexpression
             of HER2 or should not express ER or PR receptors by either IHC or in-situ
             hybridization (ISH) as defined in the relevant ASCO/CAP guidelines (Wolff et al.
             2013).

          -  Inflammatory breast cancer

          -  Newly diagnosed endocrine naïve patients

          -  No molecular evidence of endocrine resistance

          -  Prior treatment with any CDK 4/6 inhibitor and/or Fulvestrant

          -  Pre-menopausal women

          -  Are currently receiving an investigational drug in a clinical trial or participating
             in any other type of medical research judged not to be scientifically or medically
             compatible with this study. If a patient is currently enrolled in a clinical trial
             involving non-approved use of a device, then agreement with the principal investigator
             is required to establish eligibility

          -  Have had major surgery within 14 days prior to enrollment to allow for post-operative
             healing of the surgical wound

          -  Have initiated bisphosphonates or approved RANK ligand therapy for breast cancer with
             osseous metastasis, if patients are received Zolendronic acid or Denosumab in the
             adjuvant manner then such patients will be allowed participate

          -  Have serious preexisting medical conditions that, in the judgment of the investigator,
             would preclude participation in this study (for example, history of major surgical
             resection involving the stomach or small bowel or preexisting Crohn's disease or
             ulcerative colitis , interstitial lung disease, severe dyspnea at rest, any
             pre-existing chronic condition resulting in baseline grade 2 or higher diarrhea)

          -  Have a personal history of any of the following conditions: syncope or cardiovascular
             etiology, ventricular tachycardia, ventricular fibrillation or sudden cardiac arrest

          -  Have a history of any other cancer (except for non-melanoma skin cancer or carcinoma
             in situ of the cervix) unless in complete remission with no therapy for a minimum of
             three years or have received an autologous or allogeneic stem-cell transplant

          -  Have an active bacterial or fungal infection or a detectable viral infection (for
             example HIV or viral hepatitis). Screening is not required for enrollment

          -  Recent therapy with a biologic agent or a monoclonal therapy is excluded. Wash out of
             at least three half-lives of monoclonal antibody would be required to be enrolled.