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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 : July 12, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Abemaciclib Drug: Tamoxifen Drug: Prophylactic Loperamide Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 234 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 14, 2016
Actual Primary Completion Date : June 15, 2018
Estimated Study Completion Date : August 2, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Tamoxifen
Administered orally

Experimental: Abemaciclib
Abemaciclib given orally Q12H. Participants may continue to receive treatment until discontinuation criteria are met.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

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.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Prophylactic Loperamide
Administered orally




Primary Outcome Measures :
  1. 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. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Approximately 36 Months) ]
  4. 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.

  5. 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


  6. PK: Mean Single Dose Concentration of Tamoxifen and Endoxifen [ Time Frame: Cycel 1 Day 1 post dose ]
    Mean single dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.

  7. PK: Multiple Dose Concentration of Tamoxifen and Endoxifen [ Time Frame: Cycle 1 Day 15, Cycel 2 Day 1, Cycel 2 Day 15, Cycel 3 Day 1 post dose ]
    Mean multiple dose concentrations of Tamoxifen and its metabolite (Endoxifen) were reported.

  8. 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.


  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02747004


  Show 60 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
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
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] January 29, 2019
Statistical Analysis Plan  [PDF] June 29, 2016


Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02747004     History of Changes
Other Study ID Numbers: 16339
I3Y-MC-JPCG ( Other Identifier: Eli Lilly and Company )
2016-000288-18 ( EudraCT Number )
First Posted: April 21, 2016    Key Record Dates
Results First Posted: July 12, 2019
Last Update Posted: July 12, 2019
Last Verified: May 1, 2019
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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://www.clinicalstudydatarequest.com/

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Loperamide
Antidiarrheals
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Gastrointestinal Agents