Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer (Next MONARCH 1)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02747004
Recruitment Status : Active, not recruiting
First Posted : April 21, 2016
Results First Posted : July 12, 2019
Last Update Posted : October 30, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE April 19, 2016
First Posted Date  ICMJE April 21, 2016
Results First Submitted Date  ICMJE June 14, 2019
Results First Posted Date  ICMJE July 12, 2019
Last Update Posted Date October 30, 2019
Actual Study Start Date  ICMJE September 14, 2016
Actual Primary Completion Date June 15, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Up to 21 Months) ]
Progression-free survival time was measured from the date of randomization to the date of investigator-determined objective progression as defined by RECIST v1.1, or death from any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available.
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
Progression Free Survival (PFS) [ Time Frame: Baseline to Objective Disease Progression or Death from Any Cause (Approximately 14 Months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2019)
  • Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Objective Disease Progression (Up to 21 Months) ]
    Objective response rate was defined as the percentage of participants with CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD (longest diameter) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 21 Months) ]
    DoR is defined as the time from the date of first evidence of a CR or PR to the date of objective progression or death from any cause, whichever is earlier as defined by Recist v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions.
  • Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 36 Months) ]
  • Pharmacokinetics (PK): Mean Single Dose Concentration of Abemaciclib and Its Metabolites [ Time Frame: Cycle (C) 1 Day (D) 1 post dose ]
    Mean single dose concentrations of Abemaciclib and its metabolites (M2 & M20) are reported.
  • Pharmacokinetics (PK): Steady State Concentration of Abemaciclib and Its Metabolites [ Time Frame: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose ]
    Mean steady state concentrations of Abemaciclib and its metabolites (M2 & M20) are reported. C=Cycle D= Day
  • PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen [ Time Frame: Cycle 1 Day 1 post dose ]
    Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.
  • PK: Multiple Dose Concentration of Tamoxifen and Endoxifen [ Time Frame: Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1 post dose ]
    Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.
  • Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [ Time Frame: Baseline, 21 Months ]
    The EORTC QLQ-C30 self-reported general cancer instrument consists of 30 items covered by 1 of 3 dimensions:
    1. Global health status/quality of life (2 items) with scores ranging from 1 (Very Poor) to 7 (Excellent).
    2. Functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), each item scores ranging from 1 (not at all) to 4 (very much)
    3. Symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial impact), each item scores ranging from 1 (not at all) to 4 (very much).
    Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function/QOL or higher levels of symptom burden.
  • Change From Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [ Time Frame: Baseline, 21 Months ]
    mBPI-sf is an 11-item instrument used as a multiple-item measure of cancer pain intensity. In addition to pain intensity (4 items), the mBPI-sf is designed for participants to record the presence of pain in general, pain relief, and pain interference with function (general activity, mood, ability to walk, ability to perform normal work, relations with others, sleep, enjoyment of life). Responses for the mBPI-sf items are captured through the use of 11-point numeric rating scales anchored at 0 (no pain or does not interfere) and 10 (pain as bad as you can imagine or completely interferes). The mBPI-sf recall period is 24 hours and typical completion time for this instrument is less than 5 minutes.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 19, 2016)
  • Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline to Objective Disease Progression (Approximately 14 Months) ]
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Approximately 14 Months) ]
  • Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 36 Months) ]
  • Pharmacokinetics (PK): Mean Steady State Exposure of Abemaciclib and its Metabolites [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  • PK: Mean Steady State Exposure of Tamoxifen and Endoxifen [ Time Frame: Postdose Cycle 1 Day 1 through Postdose Cycle 3 Day 1 (28 Day Cycles) ]
  • Change From Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [ Time Frame: Baseline, End of Study (Approximately 14 Months) ]
  • Change from Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [ Time Frame: Baseline, End of Study (Approximately 14 Months) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer
Official Title  ICMJE A Randomized, Open-Label, Phase 2 Study of Abemaciclib Plus Tamoxifen or Abemaciclib Alone, in Women With Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer
Brief Summary The main purpose of this study is to evaluate the safety and efficacy of abemaciclib plus tamoxifen or abemaciclib alone in women with previously treated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), metastatic breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Breast Cancer
Intervention  ICMJE
  • Drug: Abemaciclib
    Administered orally
    Other Name: LY2835219
  • Drug: Tamoxifen
    Administered orally
  • Drug: Prophylactic Loperamide
    Administered orally
Study Arms  ICMJE
  • Experimental: Abemaciclib + Tamoxifen
    Abemaciclib given orally every 12 hours (Q12H) in combination with tamoxifen given orally every day. Participants may continue to receive treatment until discontinuation criteria are met.
    Interventions:
    • Drug: Abemaciclib
    • Drug: Tamoxifen
  • Experimental: Abemaciclib
    Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met.
    Intervention: Drug: Abemaciclib
  • Experimental: Abemaciclib + Prophylactic Loperamide
    Abemaciclib given orally Q12H in combination with prophylactic loperamide given orally. Participants may continue to receive treatment until discontinuation criteria are met.
    Interventions:
    • Drug: Abemaciclib
    • Drug: Prophylactic Loperamide
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 14, 2019)
234
Original Estimated Enrollment  ICMJE
 (submitted: April 19, 2016)
225
Estimated Study Completion Date  ICMJE August 2, 2021
Actual Primary Completion Date June 15, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a diagnosis of HR+, HER2- breast cancer.
  • Relapsed or progressed following endocrine therapy.
  • Have received prior treatment with at least 2 chemotherapy regimens, of which at least 1 but no more than 2 have been administered in the metastatic setting.
  • Have the presence of measureable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
  • Have a performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy.
  • Have adequate organ function.
  • Have negative serum pregnancy test within 7 days prior to the first dose of study treatment and agree to use highly effective precautions to prevent pregnancy during the study and for 3 weeks following last dose of study treatment.
  • Are able to swallow oral medication.

Exclusion Criteria:

  • Have clinical evidence or history of central nervous system metastasis.
  • Have a personal history of any of the following conditions: syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
  • Have active bacterial or fungal infection (that is, requiring intravenous antibiotics at the time of initiating study treatment) and/or detectable viral infection.
  • Have received treatment with a prior cyclin-dependent kinase (CDK4) and CDK 6 inhibitor.
  • Have a preexisting chronic condition resulting in persistent diarrhea.
  • Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix or breast), unless in complete remission with no therapy for a minimum of 3 years.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Mexico,   Argentina,   Austria,   Belgium,   Brazil,   Czechia,   France,   Germany,   Italy,   Russian Federation,   Spain,   Taiwan,   Turkey,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02747004
Other Study ID Numbers  ICMJE 16339
I3Y-MC-JPCG ( Other Identifier: Eli Lilly and Company )
2016-000288-18 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date September 1, 2019

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