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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2015 by Eli Lilly and Company
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT02057133
First received: February 4, 2014
Last updated: February 24, 2015
Last verified: February 2015
  Purpose

The main purpose of this study is to evaluate the safety of a study drug known as LY2835219 in combination with different standard therapies (letrozole, anastrozole, tamoxifen, exemestane, exemestane plus everolimus, or trastuzumab) for breast cancer that has spread to other parts of the body. The combination of LY2835219 plus trastuzumab was added as a study treatment (by protocol amendment).


Condition Intervention Phase
Breast Neoplasms
Drug: LY2835219
Drug: Letrozole
Drug: Anastrozole
Drug: Tamoxifen
Drug: Exemestane
Drug: Everolimus
Drug: Trastuzumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Study of Abemaciclib in Combination With Therapies for Patients With Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Number of Participants with One or More Drug-Related Adverse Events [ Time Frame: Baseline through study completion (estimated as 12 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics: Maximum Concentration (Cmax) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, and Transtuzumab [ Time Frame: Cycle 1 - Day 1: Predose through 10 hours post dose and Day 15: Predose. Cycle 2 - Day 1: Predose through 10 hours post dose. Cycles 3 to Cycle 5-Day1: Predose and immediately at end of infusion for Part F only. ] [ Designated as safety issue: No ]
  • Number of Participants with a Complete or Partial Tumor Response (Overall Response Rate) [ Time Frame: Baseline to study completion (estimated as 12 months) ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) [ Time Frame: First dose to progressive disease or death of any cause (estimated as 12 months) ] [ Designated as safety issue: No ]
  • Change in MD Anderson Symptom Inventory (MDASI) Score from Baseline [ Time Frame: Baseline, through study completion (estimated as 12 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, Everolimus, and Trastuzumab [ Time Frame: Cycle 1: Day 1 Predose through 10 hours post dose and Day 15 Predose. Cycle 2: Day 1 Predose through 10 hours post dose. Cycles 3 to Cycle 5-Day1: Predose and immediately at end of infusion for Part F only. ] [ Designated as safety issue: No ]

Estimated Enrollment: 102
Study Start Date: March 2014
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2835219 + Letrozole
LY2835219 orally every 12 hours in combination with letrozole 2.5 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Letrozole
Administered orally.
Experimental: LY2835219 + Anastrozole
LY2835219 orally every 12 hours in combination with anastrozole 1 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Anastrozole
Administered orally.
Experimental: LY2835219 + Tamoxifen
LY2835219 orally every 12 hrs in combination with tamoxifen 20 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Tamoxifen
Administered orally.
Experimental: LY2835219 + Exemestane
LY2835219 orally every 12 hours in combination with exemestane 25 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Exemestane
Administered orally.
Experimental: LY2835219 Dose #1 + Exemestane + Everolimus
LY2835219 dose # 1 orally every 12 hours in combination with exemestane 25 mg and everolimus 5 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Exemestane
Administered orally.
Drug: Everolimus
Administered orally.
Experimental: LY2835219 Dose #2 + Exemestane + Everolimus
LY2835219 dose #2 orally every 12 hours in combination with exemestane 25 mg and everolimus 5 mg orally once daily in 28 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Exemestane
Administered orally.
Drug: Everolimus
Administered orally.
Experimental: LY2835219 Dose #1 + Trastuzumab
LY2835219 dose #1 orally every 12 hours in combination with trastuzumab 6-8 mg/kg IV infusion once every 3 weeks in 21 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Trastuzumab
Administered IV infusion.
Experimental: LY2835219 Dose #2 + Trastuzumab
LY2835219 dose #2 orally every 12 hours in combination with trastuzumab 6-8 mg/kg IV infusion once every 3 weeks in 21 day cycles. Participants may remain on treatment until discontinuation criteria are met.
Drug: LY2835219
Administered orally.
Other Name: abemaciclib
Drug: Trastuzumab
Administered IV infusion.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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.
  • 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.
  • Have a diagnosis of HER2 positive metastatic breast cancer for Part F.
  • 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
  • Have either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  • For Parts A-E: 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.
  • 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: 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-E: Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
  • Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study (for example, history of major surgical resection involving the stomach or small bowel).
  • Have central nervous system (CNS) metastasis and 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.
  • For Part F - Cardiac disease including myocardial infarction within 6 months, unstable angina, or New York Heart Association (NYHA) Grade II or greater functional impairment.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057133

Contacts
Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Locations
United States, Arkansas
Highlands Oncology Group Recruiting
Fayetteville, Arkansas, United States, 72703
Contact    479-587-1700      
Principal Investigator: Joseph Beck         
United States, California
University of California - San Diego Recruiting
La Jolla, California, United States, 92037
Contact    858-822-6135      
Principal Investigator: Teresa Helsten         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact    617-632-6767      
Principal Investigator: Sara Tolaney         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact    507-266-6264      
Principal Investigator: Matthew Goetz         
United States, New York
Columbia University College of Phys & Surgeons Recruiting
New York, New York, United States, 10032
Contact    212-305-1945      
Principal Investigator: Kevin Kalinsky         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact    646-888-4546      
Principal Investigator: Maura Dickler         
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact    919-843-7714      
Principal Investigator: E. Claire Dees         
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact    405-271-4022      
Principal Investigator: Shubham Pant         
United States, Oregon
Providence Cancer Center Oncology Hematology Care Recruiting
Portland, Oregon, United States, 97213
Contact    506-216-8636      
Principal Investigator: Alison Conlin         
United States, Pennsylvania
Univ of Pittsburgh Cancer Inst. (UPCI) Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact    412-641-3494      
Principal Investigator: Shannon Puhalla         
United States, South Carolina
Clinical Research Unit (ITOR) Greenville Hospital System Recruiting
Greenville, South Carolina, United States, 29605
Principal Investigator: William Edenfield         
United States, Tennessee
Sarah Cannon Cancer Center Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-327-7212      
Principal Investigator: Sarah Cannon Research Inst.         
Tennessee Oncology PLLC Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-329-7274      
Principal Investigator: Howard Burris         
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact    615-936-3524      
Principal Investigator: Brent Rexer         
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact    214-370-1949      
Principal Investigator: Carlos Becerra         
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact    210-593-5250      
Principal Investigator: Muralidhar Beeram         
US Oncology Recruiting
The Woodlands, Texas, United States, 77380
Contact    281-863-1000      
Principal Investigator: US Oncology         
Texas Oncology-Baylor Charles A. Sammons Cancer Center Recruiting
Tyler, Texas, United States, 75702
Contact    903-579-9869      
Principal Investigator: David Richards         
United States, Virginia
Virginia Oncology Associates Recruiting
Norfolk, Virginia, United States, 23502
Principal Investigator: Paul Conkling         
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
  More Information

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02057133     History of Changes
Other Study ID Numbers: 15252, I3Y-MC-JPBH
Study First Received: February 4, 2014
Last Updated: February 24, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Anastrozole
Everolimus
Exemestane
Sirolimus
Trastuzumab
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on March 25, 2015