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

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02057133

Collaborator

(none)

198

Enrollment

Locations

Arms

114.4

Anticipated Duration (Months)

12.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Mar 10, 2014

Actual Primary Completion Date :

Mar 15, 2021

Anticipated Study Completion Date :

Sep 20, 2023

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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: 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 Names: Abemaciclib Drug: Endocrine therapy Endocrine therapy administered orally.

Outcome Measures

Primary Outcome Measures

Number of Participants with One or More Drug-Related Adverse Events [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 [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) [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) [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 [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 [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Highlands Oncology Group	Fayetteville	Arkansas	United States	72703
2	University of California - San Diego	La Jolla	California	United States	92037-0845
3	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	Mayo Clinic	Rochester	Minnesota	United States	55905-0002
5	Columbia University College of Phys & Surgeons	New York	New York	United States	10032
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
8	Peggy and Charles Stephenson Oklahoma Cancer Center	Oklahoma City	Ohio	United States	73104
9	Providence Cancer Center Oncology Hematology Care	Portland	Oregon	United States	97213
10	Univ of Pittsburgh Cancer Inst. (UPCI)	Pittsburgh	Pennsylvania	United States	15213
11	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
12	Tennessee Oncology PLLC	Nashville	Tennessee	United States	37203
13	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-6307
14	Texas Oncology-Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
15	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas	United States	78229-3307
16	US Oncology	The Woodlands	Texas	United States	77380

Sponsors and Collaborators

Eli Lilly and Company

Investigators

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