Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Abemaciclib and Endocrine Therapy in Older Patients With Breast Cancer.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04305834
Recruitment Status : Recruiting
First Posted : March 12, 2020
Last Update Posted : March 9, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

Tracking Information
First Submitted Date  ICMJE March 2, 2020
First Posted Date  ICMJE March 12, 2020
Last Update Posted Date March 9, 2022
Actual Study Start Date  ICMJE March 25, 2020
Estimated Primary Completion Date December 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
Incidence of grade 3 or higher toxicities [ Time Frame: Up to 30 days post treatment ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 21, 2020)
  • Incidence of toxicities [ Time Frame: Up to 30 days post treatment ]
    Toxicities will be graded and named according to CTCAE v. 5.0.
  • Incidence of toxicities [ Time Frame: Up to cycle 6 ]
    Toxicities will be captured by Patient Reported Outcome (PRO)-CTCAE.
  • Dose reductions [ Time Frame: Up to cycle 6 ]
    Will assess rates of dose reductions.
  • Dose holds [ Time Frame: Up to 30 days post treatment ]
    Will assess rates of dose holds.
  • Treatment discontinuations due to factors other than progression [ Time Frame: Up to 30 days post treatment ]
    Will assess rates of treatment discontinuations.
  • Hospitalizations [ Time Frame: Up to 2 years post treatment ]
    Will assess rates of hospitalizations.
  • Time to end of treatment [ Time Frame: Up to end of treatment ]
    Will estimate median (and 95% confidence interval [CI]) failure-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Progression free survival [ Time Frame: Up to 2 years post treatment ]
    Will estimate median (and 95% CI) progression-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Overall survival [ Time Frame: Up to 2 years post treatment ]
    Will estimate median (and 95% CI) overall survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Was It Worth It (WIWI) response [ Time Frame: Up to end of treatment ]
    Will be assessed using the WIWI questionnaire.
  • Overall treatment utility (OTU) response [ Time Frame: Up to end of treatment ]
    Will be assessed using the OTU questionnaire.
  • Adherence to abemaciclib [ Time Frame: Up to end of treatment ]
    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.
  • Average plasma steady-state abemaciclib C-trough concentrations [ Time Frame: Up to 2 years post treatment ]
  • Pharmacokinetic (PK) parameter of plasma trough concentration [ Time Frame: Up to 2 years post treatment ]
    Will evaluate the association of adherence rate with abemaciclib plasma trough concentrations.
  • Geriatric assessment scores [ Time Frame: Up to 2 years post treatment ]
    Domains include: functional status, co-morbid medical conditions, cognitive function, nutritional status, social support and psychological state, and a review of medications.
  • Incidence of toxicities attributable to agent [ Time Frame: Up to 2 years post treatment ]
    Graded by CTCAE v 5.0.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Incidence of toxicities [ Time Frame: Up to 30 days post treatment ]
    Toxicities will be graded and named according to CTCAE v. 5.0.
  • Incidence of toxicities [ Time Frame: At the beginning of each cycle, up to Cycle 6 (each cycle is 28 days) ]
    Toxicities will be captured by Patient Reported Outcome (PRO)-CTCAE.
  • Dose changes [ Time Frame: At the beginning of each cycle, and up to 30 days post treatment (each cycle is 28 days) ]
    The percentage of patients that had at least one dose change.
  • Dose holds [ Time Frame: Up to 30 days post treatment ]
    The percentage of patients that had at least one dose hold
  • Treatment discontinuations due to factors other than progression [ Time Frame: Up to 30 days post treatment ]
    Will assess rates of treatment discontinuations.
  • Hospitalizations [ Time Frame: Up to 2 years post treatment ]
    Will assess rates of hospitalizations.
  • Time to end of treatment [ Time Frame: Immediately after treatment discontinuation ]
    Will estimate median (and 95% confidence interval [CI]) failure-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Progression free survival [ Time Frame: Up to 2 years post treatment ]
    Will estimate median (and 95% CI) progression-free survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Overall survival [ Time Frame: Up to 2 years post treatment ]
    Will estimate median (and 95% CI) overall survival using Kaplan-Meier estimates and through Cox regression to adjust for covariates.
  • Was It Worth It (WIWI) response [ Time Frame: Immediately after treatment discontinuation ]
    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)
  • Overall Treatment Utility (OTU) response [ Time Frame: immediately after treatment discontinuation ]
    The patient will be given either an overall score of "good", 'intermediate", or "poor"
  • Adherence to abemaciclib [ Time Frame: Baseline, Immediately after treatment discontinuation ]
    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.
  • Average plasma steady-state abemaciclib C-trough concentrations [ Time Frame: Up to 2 years post treatment ]
  • Pharmacokinetic (PK) parameter of plasma trough concentration [ Time Frame: Up to 2 years post treatment ]
    Will evaluate the association of adherence rate with abemaciclib plasma trough concentrations.
  • Geriatric assessment scores [ Time Frame: Up to 2 years post treatment ]
    The average and standard deviation for geriatric assessment scores will be assessed
  • Incidence of toxicities attributable to agent [ Time Frame: Up to 2 years post treatment ]
    Graded by CTCAE v 5.0.
Current Other Pre-specified Outcome Measures
 (submitted: May 21, 2020)
  • Biological age via deoxyribonucleic acid (DNA) methylation level [ Time Frame: Up to 2 years post treatment ]
  • Genome-wide methylome and transcriptome analyses [ Time Frame: Up to 2 years post treatment ]
  • Incidence of toxicities at least possibly attributable to agent [ Time Frame: Up to 2 years post treatment ]
    Graded by CTCAE v 5.0.
Original Other Pre-specified Outcome Measures
 (submitted: March 10, 2020)
  • Biological age via deoxyribonucleic acid (DNA) methylation level [ Time Frame: Up to 2 years post treatment ]
  • Genome-wide methylome and transcriptome analyses [ Time Frame: Up to 2 years post treatment ]
  • Incidence of toxicities 8at least possibly attributable to agent [ Time Frame: Up to 2 years post treatment ]
    Graded by CTCAE v 5.0.
 
Descriptive Information
Brief Title  ICMJE Abemaciclib and Endocrine Therapy in Older Patients With Breast Cancer.
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Anatomic Stage IV Breast Cancer AJCC v8
  • Hormone Receptor Positive Breast Carcinoma
  • Metastatic Breast Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8
Intervention  ICMJE
  • Drug: Abemaciclib
    Given PO
    Other Names:
    • LY-2835219
    • LY2835219
    • Verzenio
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE Experimental: Treatment (abemaciclib)
Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Abemaciclib
  • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 15, 2023
Estimated Primary Completion Date December 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 70 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04305834
Other Study ID Numbers  ICMJE 19206
NCI-2019-08847 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
19206 ( Other Identifier: City of Hope Medical Center )
P30CA033572 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party City of Hope Medical Center
Original Responsible Party Same as current
Current Study Sponsor  ICMJE City of Hope Medical Center
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Mina S Sedrak City of Hope Medical Center
PRS Account City of Hope Medical Center
Verification Date March 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP