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

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ClinicalTrials.gov Identifier: NCT02057133

Recruitment Status : Active, not recruiting

First Posted : February 6, 2014

Last Update Posted : March 25, 2024

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Sponsor:

Information provided by (Responsible Party):

Eli Lilly and Company

Study Description

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 :	December 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Abemaciclib

U.S. FDA Resources

Arms and Interventions

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

Primary Outcome Measures :

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 :

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

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

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United States, Arkansas
Highlands Oncology Group - Duplicate 2
Rogers, Arkansas, United States, 72758
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, 37203
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
Tennessee Oncology PLLC
Nashville, Tennessee, United States, 37203
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-6307
United States, Texas
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, United States, 78229-3307

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

Additional Information:

Click here for more information about this study: A Study of Abemaciclib (LY2835219) in Combination With Other Therapies in Participants With Breast Cancer That Has Spread This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

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

Tolaney SM, Beeram M, Beck JT, Conlin A, Dees EC, Puhalla SL, Rexer BN, Burris HA, Jhaveri K, Helsten T, Becerra C, Kalinsky K, Moore KN, Manuel AM, Lithio A, Price GL, Chapman SC, Litchfield LM, Goetz MP. Abemaciclib in Combination With Endocrine Therapy for Patients With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Phase 1b Study. Front Oncol. 2022 Feb 10;11:810023. doi: 10.3389/fonc.2021.810023. eCollection 2021.

Gelbert LM, Cai S, Lin X, Sanchez-Martinez C, Del Prado M, Lallena MJ, Torres R, Ajamie RT, Wishart GN, Flack RS, Neubauer BL, Young J, Chan EM, Iversen P, Cronier D, Kreklau E, de Dios A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37. doi: 10.1007/s10637-014-0120-7. Epub 2014 Jun 13.

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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:	March 25, 2024
Last Verified:	March 2024

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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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

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