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Neo-adjuvant Abemaciclib with Fulvestrant for the Treatment of Hormone Receptor Positive Stage I-III Breast Cancer

Trial Status: Approved

This phase II trial studies how well abemaciclib and fulvestrant work before surgery (neo-adjuvant) in treating patients with hormone receptor positive stage I-III breast cancer that has come back in the breast and has not spread to other distant organs (localized non-metastatic breast cancer) and demonstrates resistance to endocrine therapy. Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast tumor cells. Fulvestrant may help fight breast cancer by blocking the use of estrogen by the tumor cells. Abemaciclib and fulvestrant may destroy as much cancer as possible that will allow a complete pathologic response to be achieved. A complete pathologic response is defined as the absence of breast cancer in the breast and / or the axillary (a person's armpit) lymph nodes in the surgical specimen.

Inclusion Criteria

  • Patients must have a diagnosis of hormone receptor (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 (estrogen receptor [ER], progesterone receptor [PgR]) as defined in the relevant American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) Guidelines: * For ER and PgR assays to be considered positive, >= 1% of tumor cell nuclei must be immunoreactive by immunohistochemistry (IHC)
  • Patients must have Loco regional breast cancer (stage I, stage II and stage III per American Joint Committee on Cancer [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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Have post-menopausal status as defined by following: * Prior bilateral oophorectomy * Age >= 60 years * 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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Hemoglobin > 8 g/dL * 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
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 X institutional upper limit of normal (ULN) * Patients with Gilbert’s syndrome with a total bilirubin =< 2.0 times ULN and direct bilirubin within normal limits are permitted
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 2.5 X institutional ULN
  • Creatinine =< 1.5 X institutional ULN
  • 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 * 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 tumor, node, metastasis (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 * 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
  • Inflammatory breast cancer
  • Newly diagnosed endocrine naive 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 zoledronic 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 human immunodeficiency virus [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


UC Irvine Health / Chao Family Comprehensive Cancer Center
Contact: Ritesh Parajuli
Phone: 714-456-8614


I. To determine if neo-adjuvant abemaciclib and fulvestrant improves a pathological complete response in patients 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.


I. To determine the objective response rate (ORR) in the breast and/or the axillary lymph nodes.

II. To determine if the combination of abemaciclib and fulvestrant increases the percentage of patients who undergo breast conserving surgery.

III. Recurrence disease-free survival.

IV. Safety and toxicity.

V. To determine the percentage change in the Ki 67 from baseline to the treated specimen after breast surgery.

VI. To determine the preoperative endocrine prognostic index (PEPI) score as predictors of response to neo-adjuvant abemaciclib and fulvestrant.


I. To determine if genomic analysis of patient matched breast tissue samples and serial mutational tracking of circulating tumor deoxyribonucleic acid (DNA) can identify new mechanisms of endocrine resistance and how abemaciclib overcomes endocrine resistance.

II. To determine the mechanism of response or resistance to abemaciclib.

III. To determine biomarkers related to the retinoblastoma (Rb) pathway.


Patients receive abemaciclib orally (PO) twice daily BID on days 1-28 and fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and on day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months after surgery for up to 5 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
UC Irvine Health / Chao Family Comprehensive Cancer Center

Principal Investigator
Ritesh Parajuli

  • Primary ID UCI 18-79
  • Secondary IDs NCI-2020-01820, 2020-5660
  • ID NCT04305236