Clinical Trials /

Abemaciclib Monotherapy in Treating Older Patients With Hormone Receptor Positive Metastatic Breast Cancer

NCT04305834

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Abemaciclib Monotherapy in Treating Older Patients With Hormone Receptor Positive Metastatic Breast Cancer
  • Official Title: A Phase IIA Trial Assessing the Tolerability of Abemaciclib Monotherapy in Patients Age 70 and Older With Hormone Receptor Positive Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19206
  • SECONDARY ID: NCI-2019-08847
  • SECONDARY ID: 19206
  • NCT ID: NCT04305834

Conditions

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Hormone Receptor Positive Breast Carcinoma
  • Metastatic Breast Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8

Interventions

DrugSynonymsArms
AbemaciclibLY-2835219, LY2835219, VerzenioTreatment (abemaciclib)

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (abemaciclib)ExperimentalPatients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Abemaciclib

Eligibility Criteria

        Inclusion Criteria:

          -  Documented informed consent of the participant

          -  Age >= 70 years

          -  Life expectancy > 6 months

          -  Ability to read and understand one or more of the following languages for
             questionnaires: English, Spanish, Chinese, Japanese, Korean, or French

          -  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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:70 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of grade 3 or higher toxicities
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:Adverse events will be characterized using the descriptions and grading scales found in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0.

Secondary Outcome Measures

Measure:Incidence of toxicities
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:Toxicities will be graded and named according to CTCAE v. 5.0.
Measure:Incidence of toxicities
Time Frame:At the beginning of each cycle, up to Cycle 6 (each cycle is 28 days)
Safety Issue:
Description:Toxicities will be captured by Patient Reported Outcome (PRO)-CTCAE.
Measure:Dose changes
Time Frame:At the beginning of each cycle, and up to 30 days post treatment (each cycle is 28 days)
Safety Issue:
Description:The percentage of patients that had at least one dose change.
Measure:Dose holds
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:The percentage of patients that had at least one dose hold
Measure:Treatment discontinuations due to factors other than progression
Time Frame:Up to 30 days post treatment
Safety Issue:
Description:Will assess rates of treatment discontinuations.
Measure:Hospitalizations
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Will assess rates of hospitalizations.
Measure:Time to end of treatment
Time Frame:Immediately after treatment discontinuation
Safety Issue:
Description:Will estimate median (and 95% confidence interval [CI]) failure-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
Measure:Progression free survival
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Will estimate median (and 95% CI) progression-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
Measure:Overall survival
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Will estimate median (and 95% CI) overall survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
Measure:Was It Worth It (WIWI) response
Time Frame:Immediately after treatment discontinuation
Safety Issue:
Description:The WIWI is comprised of 5 dimensions, and each dimension has three levels. Was it worthwhile for you to undergo cancer treatment? (Yes, No, or Uncertain); If you had to do it over, would you undergo cancer treatment (Yes, No, or Uncertain);Would you recommend this cancer treatment to others? (Yes, No, or Uncertain); Overall, did you quality of life change by undergoing cancer treatment? (It improved, It stayed the same, It got worse); Overall how was your experience following cancer treatment? (Better than I expected, The same as I expected; Worse than I expected)
Measure:Overall Treatment Utility (OTU) response
Time Frame:immediately after treatment discontinuation
Safety Issue:
Description:The patient will be given either an overall score of "good", 'intermediate", or "poor"
Measure:Adherence to abemaciclib
Time Frame:Baseline, Immediately after treatment discontinuation
Safety Issue:
Description:Adherence defined as taking 90% of scheduled doses per cycle. Scheduled doses are assigned doses for the participant which may vary per participant depending on whether or not there a hold in treatment. Adherence will be calculated based on consolidation of pill diary with returned unused pills, and, for City of Hope (COH) Duarte patients, Medication Event Monitoring bottle caps.
Measure:Average plasma steady-state abemaciclib C-trough concentrations
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:
Measure:Pharmacokinetic (PK) parameter of plasma trough concentration
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Will evaluate the association of adherence rate with abemaciclib plasma trough concentrations.
Measure:Geriatric assessment scores
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:The average and standard deviation for geriatric assessment scores will be assessed
Measure:Incidence of toxicities attributable to agent
Time Frame:Up to 2 years post treatment
Safety Issue:
Description:Graded by CTCAE v 5.0.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

March 10, 2020