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A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread

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: NCT02057133
Recruitment Status : Active, not recruiting
First Posted : February 6, 2014
Last Update Posted : April 18, 2023
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Description
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Brief Summary:
This study evaluates the safety of abemaciclib in combination therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, trastuzumab, LY3023414 plus fulvestrant, pertuzumab plus trastuzumab with loperamide, or ongoing endocrine therapy) for breast cancer that has spread to other parts of the body.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Drug: LY2835219 Drug: Letrozole Drug: Anastrozole Drug: Tamoxifen Drug: Exemestane Drug: Everolimus Drug: Trastuzumab Drug: LY3023414 Drug: Fulvestrant Drug: Pertuzumab Drug: Loperamide Drug: Endocrine therapy Phase 1

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

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 198 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer
Actual Study Start Date : March 10, 2014
Actual Primary Completion Date : March 15, 2021
Estimated Study Completion Date : September 20, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Abemaciclib

Arms and Interventions
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Arm Intervention/treatment
Experimental: LY2835219 + Letrozole
LY2835219 administered orally. Letrozole administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Letrozole
Administered orally.
Experimental: LY2835219 + Anastrozole
LY2835219 administered orally. Anastrozole administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Anastrozole
Administered orally.
Experimental: LY2835219 + Tamoxifen
LY2835219 administered orally. Tamoxifen administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Tamoxifen
Administered orally.
Experimental: LY2835219 + Exemestane
LY2835219 administered orally. Exemestane administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Exemestane
Administered orally.
Experimental: LY2835219 + Exemestane + Everolimus Dose Escalation
LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Exemestane
Administered orally.

Drug: Everolimus
Administered orally.
Experimental: LY2835219 + Exemestane + Everolimus Dose Expansion
LY2835219 administered orally. Exemestane administered orally. Everolimus administered orally. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Exemestane
Administered orally.

Drug: Everolimus
Administered orally.
Experimental: LY2835219+ Trastuzumab Dose Escalation
LY2835219 administered orally. Trastuzumab administered intravenously (IV) infusion. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Trastuzumab
Administered IV infusion.
Experimental: LY2835219+ Trastuzumab Dose Expansion
LY2835219 administered orally. Trastuzumab administered IV infusion. This arm is closed to enrollment.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Trastuzumab
Administered IV infusion.
Experimental: LY3023414 + LY2835219 + Fulvestrant Dose Escalation
LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered intramuscularly (IM).
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: LY3023414
Administered orally.

Drug: Fulvestrant
Administered IM.
Experimental: LY3023414 + LY2835219 + Fulvestrant Dose Expansion
LY3023414 administered orally. LY2835219 administered orally. Fulvestrant administered IM.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: LY3023414
Administered orally.

Drug: Fulvestrant
Administered IM.
Experimental: LY2835219 +Trastuzumab +Pertuzumab +Loperamide Dose Escalation
LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Trastuzumab
Administered IV infusion.

Drug: Pertuzumab
Administered IV infusion.

Drug: Loperamide
Administered orally.
Experimental: LY2835219 +Trastuzumab + Pertuzumab +Loperamide Dose Expansion

Hormone Receptor Negative (HR-): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion.

Hormone Receptor Positive (HR+): LY2835219 administered orally. Loperamide administered orally. Trastuzumab administered IV infusion. Pertuzumab administered IV infusion. Endocrine therapy administered orally.

 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Trastuzumab
Administered IV infusion.

Drug: Pertuzumab
Administered IV infusion.

Drug: Loperamide
Administered orally.

Drug: Endocrine therapy
Endocrine therapy administered orally.
Experimental: LY2835219 + Endocrine Therapy
LY2835219 administered orally. Ongoing endocrine therapy administered orally.
 Drug: LY2835219
Administered orally.
Other Name: Abemaciclib

Drug: Endocrine therapy
Endocrine therapy administered orally.


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with One or More Drug-Related Adverse Events [ Time Frame: Baseline through study completion (estimated as 12 months) ]
    Number of participants with one or more drug-related adverse events


Secondary Outcome Measures :
  1. Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab [ Time Frame: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part. ]
    Cmax of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.

  2. Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [ Time Frame: Baseline to study completion (estimated as 12 months) ]
    Number of participants with a complete or partial tumor response (overall response rate).

  3. Progression Free Survival (PFS) [ Time Frame: First dose to progressive disease or death of any cause (estimated as 12 months) ]
    Progression free survival

  4. Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline [ Time Frame: Baseline, through study completion (estimated as 12 months) ]
    Change in MD Anderson (MDASI) score from baseline.

  5. Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, Trastuzumab, LY3023414, Fulvestrant, and Pertuzumab [ Time Frame: Cycle 1 up to Cycle 5 (21 or 28 Day Cycle): Predose and at multiple timepoints, depending on study part. ]
    Pharmacokinetics: AUC of LY2835219, letrozole, anastrozole, tamoxifen, exemestane, everolimus, trastuzumab, LY3023414, fulvestrant, and pertuzumab.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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 hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer for Parts A to E, G, and I.
  • Have a diagnosis of human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer for Parts F and H.
  • For Part A (LY2835219 + letrozole): Except for ongoing therapy with letrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
  • For Part B (LY2835219 + anastrozole): Except for ongoing therapy with anastrozole, the participant must not have received prior systemic endocrine therapy for metastatic disease.
  • For Part C (LY2835219 + tamoxifen): The participant may have received prior systemic endocrine therapy for metastatic disease and may be receiving ongoing therapy with tamoxifen.
  • For Part D (LY2835219 + exemestane): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with exemestane.
  • For Part E (LY2835219 + exemestane + everolimus): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus.
  • For Part F (LY2835219 + trastuzumab):The participant must have received at least 1 chemotherapy regimen for metastatic disease and may be receiving ongoing therapy with trastuzumab. The participant must have an estimated left ventricular ejection fraction within the normal range by either echocardiogram or multigated acquisition (MUGA) scan
  • For Part G (abemaciclib + LY3023414 + fulvestrant): The participant may have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease.
  • For Part H: (abemaciclib + trastuzumab + pertuzumab): The participant must have received at least 1 chemotherapy regimen for metastatic disease. The participant may be receiving ongoing therapy with trastuzumab and/or pertuzumab at the time of study entry. The participant must have an estimated left ventricular ejection fraction (LVEF) within the normal range by either echocardiogram or multigated acquisition (MUGA) scan.
  • For Part I (abemaciclib + endocrine therapy): The participant must have demonstrated evidence of disease progression on a Cyclin Dependent Kinase 4 (CDK4) and Cyclin Dependent Kinase 6 (CDK6) inhibitor (either palbociclib or ribociclib) plus endocrine therapy for advanced or metastatic disease as the most recent therapy immediately preceding study entry. The participant should remain on the current endocrine therapy while receiving abemaciclib.
  • For Parts A, B, C, D, E, and F: Have either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  • For Part G, H, and I: Have measureable disease as defined by RECIST 1.1.
  • For all Parts except Part F and H: Participants must have either post-menopausal status or pre-menopausal status if continuing or beginning ovarian suppression with a luteinizing hormone-releasing hormone (LHRH) agonist such as goserelin.
  • Parts H, and I: Must be able and willing to undergo mandatory tumor biopsies prior to study treatment and at the time of discontinuation from study treatment.

  • Have adequate organ function, including:

    • Hematologic: Absolute neutrophil count (ANC) ≥1.5 x 10^9/liter (L), platelets ≥ 100 x 10^9/L, and hemoglobin ≥ 8 gram/deciliter (g/dL).
    • Hepatic: Bilirubin ≤1.5 times upper limits of normal (ULN), alanine aminotransferase (ALT) ≤ 3.0 times ULN.
    • Renal: Serum creatinine ≤ 1.5 times ULN.
  • Have a performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale.
  • Have discontinued all previous therapies for breast cancer (including chemotherapy, radiotherapy, immunotherapy, and investigational therapy), except for ongoing corresponding combination therapy, for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug(s), 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. For Part F and H: concurrent treatment with trastuzumab emtansine (T-DM1) is not allowed.

Exclusion Criteria:

  • Have metastatic breast cancer with severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
  • Have brain metastasis without prior radiotherapy.
  • For Parts A, B, C, D, E, G and I: Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
  • For Parts A, B, C, D, E, F, H: Have received prior therapy with a CDK4/6 inhibitor, Part G: Have received prior therapy with fulvestrant or any PI3K and/or mTOR inhibitor (including LY3023414); Part I: Have received prior treatment with abemaciclib in any setting.
  • Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (including interstitial lung disease (ILD), severe dyspnea at rest or requiring oxygen therapy or, history of major surgical resection involving the stomach or small bowel).
  • Have central nervous system (CNS) metastasis with either radiotherapy or development of neurological changes ≤14 days prior to receiving study treatment. Participants may be receiving a stable dose of corticosteroids. Screening of asymptomatic participants without history of CNS metastasis is not required. Untreated CNS metastases are not permitted.
  • For Parts F and H: Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment.
  • For Part G: Have type 1 diabetes mellitus or a history of gestational diabetes mellitus. Participants with a type 2 diabetes mellitus are eligible if adequate control of blood glucose level is obtained with oral therapy as documented by Hemoglobin A1c <7%.
  • For Part G: Have a baseline electrocardiogram (obtained from Day -14 to Day -1) with any of the following abnormal findings: ventricular arrhythmia, evidence of acute myocardial ischemia, heart block (of any degree), or QTc prolongation (defined as QTcB ≥450 milliseconds).
Contacts and Locations
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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): NCT02057133


Locations
Layout table for location information
United States, Arkansas
Highlands Oncology Group
Fayetteville, Arkansas, United States, 72703
United States, California
University of California - San Diego
La Jolla, California, United States, 92037-0845
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905-0002
United States, New York
Columbia University College of Phys & Surgeons
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27514
United States, Ohio
Peggy and Charles Stephenson Oklahoma Cancer Center
Oklahoma City, Ohio, United States, 73104
United States, Oregon
Providence Cancer Center Oncology Hematology Care
Portland, Oregon, United States, 97213
United States, Pennsylvania
Univ of Pittsburgh Cancer Inst. (UPCI)
Pittsburgh, Pennsylvania, United States, 15213
United States, Tennessee
Sarah Cannon Cancer Center
Nashville, Tennessee, United States, 37203
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6307
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States, 78229-3307
US Oncology
The Woodlands, Texas, United States, 77380
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
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02057133    
Other Study ID Numbers: 15252
I3Y-MC-JPBH ( Other Identifier: Eli Lilly and Company )
First Posted: February 6, 2014    Key Record Dates
Last Update Posted: April 18, 2023
Last Verified: April 2023

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Trastuzumab
Pertuzumab
Everolimus
Letrozole
Fulvestrant
Anastrozole
Exemestane
Loperamide
Antineoplastic Agents, Immunological
 Antineoplastic Agents
MTOR Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators