Abemaciclib and Endocrine Therapy in Older Patients With Breast Cancer.

City of Hope

Status and phase

Enrolling

Phase 2

Conditions

Anatomic Stage IV Breast Cancer AJCC v8

Prognostic Stage IV Breast Cancer AJCC v8

Metastatic Breast Carcinoma

Hormone Receptor Positive Breast Carcinoma

Treatments

Other: Questionnaire Administration

Drug: Abemaciclib

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04305834

NCI-2019-08847 (Registry Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

19206

Details and patient eligibility

About

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.

Full description

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.

Enrollment

43 estimated patients

Sex

All

Ages

70+ years old

Volunteers

No Healthy Volunteers

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