PRIMARY OBJECTIVE:
I. To estimate the incidence of grade 3 or higher toxicities attributed to abemaciclib
monotherapy in adults aged 70 or older with hormone receptor positive metastatic breast
cancer.
SECONDARY OBJECTIVES:
I. To describe the full toxicity profile including all grade 2 and higher adverse events, and
patient-reported adverse events (AEs) using Patients Reported Outcomes (PRO)-Common
Terminology Criteria for Adverse Events (CTCAE) measures.
II. To describe rates of dose reductions, dose holds, treatment discontinuations due to
factors other than progression, and hospitalizations.
III. To estimate median (and 95% confidence interval [CI]) failure-free survival,
progression-free survival and overall survival.
IV. To describe the results of Was It Worth It (WIWI) and Overall Treatment Utility (OTU)
questionnaires.
V. To describe the rate of adherence to abemaciclib. VI. To determine average plasma
steady-state abemaciclib Ctrough concentrations.
VII. To evaluate the association of adherence rate with abemaciclib plasma t-rough
concentrations.
VIII. To describe associations between cancer-specific, comprehensive Geriatric Assessment
(cGA) scores and the incidence of toxicities and their grade.
EXPLORATORY OBJECTIVE:
I. To determine the association between biomarkers of aging and grades 3 or higher toxicity.
OUTLINE:
Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every
28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 6 months
for 2 years.
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
radiotherapy)
- 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
therapy
- 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
metastases
- 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
formula
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
enrollment
- 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
