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Trial record 1 of 1 for:    neoMONARCH
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A Neoadjuvant Study of Abemaciclib (LY2835219) in Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Breast Cancer (neoMONARCH)

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: NCT02441946
Recruitment Status : Completed
First Posted : May 12, 2015
Results First Posted : January 30, 2018
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The purpose of this study is to evaluate the biological effects of abemaciclib in combination with anastrozole and compare those to the effects of abemaciclib alone and anastrozole alone in the tumors of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Hormone Receptor Positive Tumor Early-Stage Breast Carcinoma Drug: Abemaciclib Drug: Loperamide Drug: Anastrozole 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 : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: neoMONARCH: A Phase 2 Neoadjuvant Trial Comparing the Biological Effects of 2 Weeks of Abemaciclib (LY2835219) in Combination With Anastrozole to Those of Abemaciclib Monotherapy and Anastrozole Monotherapy and Evaluating the Clinical Activity and Safety of a Subsequent 14 Weeks of Therapy With Abemaciclib in Combination With Anastrozole in Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Breast Cancer
Study Start Date : August 2015
Actual Primary Completion Date : August 16, 2016
Actual Study Completion Date : February 12, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Abemaciclib + Anastrozole

Abemaciclib (150 milligrams [mg]) was given orally every 12 hours (Q12H) plus anastrozole (1 mg) orally once daily (QD) for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion.

All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks.

Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Loperamide
Administered orally

Drug: Anastrozole
Administered orally

Experimental: Abemaciclib

Abemaciclib (150 mg) was given orally Q12H for 2 weeks. Loperamide was given as a prophylaxis for 4 weeks and then at physician discretion.

All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Total treatment duration was 16 weeks.

Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Loperamide
Administered orally

Drug: Anastrozole
Administered orally

Active Comparator: Anastrozole

Anastrozole (1 mg) is given orally QD for 2 weeks.

All participants received abemaciclib (150 mg) orally Q12H plus anastrozole (1 mg) QD for an additional 14 weeks. Loperamide was given as a prophylaxis for the first 2 weeks of the combination treatment and then at physician discretion. Total treatment duration was 16 weeks.

Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Loperamide
Administered orally

Drug: Anastrozole
Administered orally




Primary Outcome Measures :
  1. Percent Change From Baseline to 2 Weeks in Ki67 Expression [ Time Frame: Baseline, 2 Weeks ]
    Tumor tissue collected through a core biopsy at baseline and at the end of cycle 1 was used to determine Ki67 expression. Ki67 expression is defined as the percent of cells staining positive by validated central assay.


Secondary Outcome Measures :
  1. Percentage of Participants With Pathologic Complete Response (pCR) [ Time Frame: From Start of Treatment Up to 16 Weeks ]
    pCR is defined as absence of invasive cancer in the breast and sampled regional lymph nodes.

  2. Percentage of Participants With Complete Response (CR) or Partial Response (PR): Clinical Objective Response [ Time Frame: From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) ]
    Clinical objective response is defined as the percentage of participants with the best overall response rate (ORR) with a best OR of CR or PR, according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1. ORR is recorded from the start of the study treatment until the earliest of objective progression or start of new anticancer therapy. A responder depends on target and non-target disease and the appearance of new lesions. CR is defined as the disappearance of all non-target lesions. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. All lymph nodes are non-pathological or normal in size (<10mm short axis). Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, a relative increase of 20%, the sum must also demonstrate an absolute increase of 5 mm.

  3. Percentage of Participants With Complete Radiologic Response or Partial Radiological Response: Radiological Response [ Time Frame: From Start of Treatment to Objective Progression or Start of New Anticancer Therapy (Up to 16 Weeks) ]
    Radiological response is the percentage of participants with CR or, PR according to RECIST v.1.1. A responder is defined as any participant who exhibits a CR or PR. CR is the disappearance of all target lesions. PR is a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. PD is 20% increase in the sum of diameters of target lesions taking as reference the smallest sum and the appearance of 1 or more new lesions.

  4. Change From Baseline to Week 2 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline, 2 Weeks ]
    EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, emotional, cognitive, or social functioning), global health status and symptom scales of fatigue, pain, nausea/vomiting, dyspnea, insomnia, appetite loss, constipation, diarrhea, or financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

  5. Pharmacokinetics (PK): Apparent Clearance of Abemaciclib [ Time Frame: Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose ]
    Abemaciclib apparent clearance (CL/F) was calculated by population nonlinear mixed effects modeling (NONMEM) using all available data spanning cycles 1 and cycles 3-5.

  6. PK: Apparent Volume of Distribution of Abemaciclib [ Time Frame: Cycle(C)1, Day(D)1: 2 to 4 Hours (Hrs) Postdose; C1D14: 4 Hrs Postdose, 7 Hrs Postdose; C3D1: Predose, 3 Hrs Postdose, C4D1 & C5D1, Predose, C5D28: Predose, 3 Hrs Postdose ]
    Abemaciclib apparent volume of distribution was calculated by population NONMEM using all available data spanning cycles 1 and cycles 3-5.



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 postmenopausal status.
  • Adenocarcinoma of the breast.
  • Breast tumor ≥1 centimeter (cm) in diameter, HR+, HER2-.
  • Neoadjuvant endocrine monotherapy is deemed to be a suitable therapy.
  • Primary breast cancer that is suitable for baseline core biopsy.
  • Have adequate organ function.

Exclusion Criteria:

  • Bilateral invasive breast cancer.
  • Metastatic breast cancer (local spread to axillary lymph nodes is permitted).
  • Inflammatory breast cancer.
  • Prior systemic therapy or radiotherapy for invasive or non-invasive breast cancer in the same breast as currently being treated.
  • Prior radiotherapy to the ipsilateral chest wall for any malignancy.
  • Prior anti-estrogen therapy.

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): NCT02441946


  Show 66 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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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

Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02441946     History of Changes
Other Study ID Numbers: 15805
I3Y-MC-JPBY ( Other Identifier: Eli Lilly and Company )
2014-005486-75 ( EudraCT Number )
First Posted: May 12, 2015    Key Record Dates
Results First Posted: January 30, 2018
Last Update Posted: September 16, 2019
Last Verified: August 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 European Union (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/
Keywords provided by Eli Lilly and Company:
cyclin-dependent kinase (CDK) 4/6 inhibitor
CDK 4 and 6 inhibitor
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Anastrozole
Loperamide
Antidiarrheals
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Gastrointestinal Agents