A Phase IIA Trial Assessing the Tolerability of Abemaciclib in Combination with Endocrine Therapy in Patients Age 70 and Older with Hormone Receptor Positive Metastatic Breast Cancer Who Have Progressed on or After Prior CDK 4/6 Inhibition

Protocol # :
Anatomic Stage IV Breast Cancer AJCC v8
Hormone Receptor Positive Breast Carcinoma
Metastatic Breast Carcinoma
Prognostic Stage IV Breast Cancer AJCC v8
Disease Sites
Principal Investigator
Freedman, Rachel, A
Site Research Nurses
Campbell, Margaret
Dishman, Rachel, C.
Ficociello, Samantha
Kasparian, Elizabeth
Orechia, Meghan
Patel, Nikita
Roche, Kathleen, A.
Rutter, Morgan

Trial Description

This phase IIa trial studies the side effects of abemaciclib monotherapy in treating patients
age 70 years and older with hormone receptor positive, HER2 negative breast cancer that has
spread to other places in the body.

Eligibility Requirements

Inclusion Criteria:

- Documented informed consent of the participant

- Age >= 70 years

- Life expectancy > 6 months

- Ability to read and understand English or Spanish

- Measurable or non-measurable disease

- Histologically or cytologically confirmed diagnosis of:

- Estrogen-receptor positive and/or progesterone receptor positive breast cancer
determined by immunohistochemistry (IHC) methods according to the local
institution standard protocol

- HER2-negative breast cancer defined as negative if the IHC status is 0 or 1+, or
if IHC is 2+ and in situ hybridization assay is negative per American Society of
Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines

- Radiographically confirmed metastatic breast cancer

- Progressed on prior endocrine therapy or palbociclib or ribociclib or chemotherapy

- Patients who received chemotherapy recovered from the acute side effects to prior
cancer therapy (except alopecia or residual grade 2 peripheral neuropathy) to =< grade
1 or baseline. A washout period of at least 21 days is required between last
chemotherapy dose and randomization (provided the patient did not receive

- Patients who received 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 randomization

- Absence of central nervous system (CNS) involvement unless they meet ONE of the
following criteria:

- Untreated brain metastases (e.g., lesions < 1 cm) not needing immediate local

- Previously treated brain metastases not needing immediate local therapy

- At least 4 weeks from the last date of prior therapy completion (including
radiation and/or surgery) to starting the study treatment

- Clinically stable CNS tumor at the time of screening and not receiving
steroids and/or enzyme-inducing anti-epileptic medications for brain

- Absence of interstitial lung disease/pneumonitis

- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

- Platelets >= 100 x 10^9/L

- Hemoglobin >= 8 g/dL

- (Patients may receive erythrocyte transfusions to achieve this hemoglobin level
at the discretion of the investigator. Initial treatment must not begin earlier
than the day after the erythrocyte transfusion)

- In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)

- If the patient has liver metastases, ALT and AST < 5 x ULN

- In patients without Gilbert's syndrome, total bilirubin =< 1.5 x ULN; In patients with
Gilbert's syndrome, total bilirubin =< 2.0 x ULN or direct bilirubin within normal
limits (WLN)

- Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault

Exclusion Criteria:

- Major surgery within 14 days prior to receiving study drug or has not recovered from
major side effect

- Patient is currently receiving any of the prohibited medications detailed below and
cannot be discontinued 7 days prior to starting study drug

- Other investigational therapy should be given to participants

- Anticancer agents other than the study medications administered as part of this
study protocol should be given to participants. If such agents are required for a
participant then the participant must first be withdrawn from the study

- Co-medication that may interfere with study results; e.g. immune-suppressive
agents other than corticosteroids, such as systemic cyclosporine and tacrolimus
are prohibited during the treatment phase of the study, unless discussed with
principal investigator felt to be of low clinical risk to the participant

- Use of herbal medications may have unknown interactions with the metabolism of
the study agents, and therefore are prohibited from use during the treatment
phase of the trial

- Known hypersensitivity to any of the excipients of abemaciclib

- Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of
initiating study treatment), fungal infection, or detectable viral infection (such as
known human immunodeficiency virus positivity or with known active hepatitis B or C
(for example, hepatitis B surface antigen positive). Screening is not required for

- Impairment of gastrointestinal (GI) function or GI disease that in the investigator's
opinion may significantly alter the absorption of the study drugs (e.g., ulcerative
diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small
bowel resection)

- History of any of the following conditions: syncope of cardiovascular etiology,
ventricular arrhythmia of pathological origin (including, but not limited to,
ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest

- Patient has any other concurrent severe or uncontrolled medical condition that would,
in the investigator's judgment, cause unacceptable safety risks, contraindicate
patient participation in the clinical study or compromise compliance with the protocol
(e.g. chronic pancreatitis, chronic active hepatitis)

- Inability to swallow oral medications

- Serious or uncontrolled preexisting medical condition(s) that, in the judgment of the
investigator, would preclude participation in this study (for example, interstitial
lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal
impairment [e.g. estimated creatinine clearance < 30 ml/min], history of major
surgical resection involving the stomach or small bowel, or preexisting Crohn's
disease or ulcerative colitis or a preexisting chronic condition resulting in baseline
grade 2 or higher diarrhea)

- History of non-compliance to medical regimen

- Patients with a prior malignancy diagnosed within 2 years and with evidence of disease
(except adequately treated, basal or squamous cell carcinoma, non-melanomatous skin
cancer or curatively resected cervical cancer