A Study of LY2835219 in Combination With Hormone Therapies for Breast Cancer That Has Spread

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 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: August 11, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Breast Neoplasms
Drug: LY2835219
Drug: Letrozole
Drug: Anastrozole
Drug: Tamoxifen
Drug: Exemestane
Drug: Everolimus
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 LY2835219 in Combination With Endocrine Therapies for Patients With Hormone Receptor Positive, HER2 Negative 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, and Everolimus [ 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 ] [ 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 measured progressive disease or death of any cause (estimated as 12 months) ] [ Designated as safety issue: No ]
  • Change from Baseline to Cycle 3 in MD Anderson Symptom Inventory (MDASI) Score [ Time Frame: Baseline, Cycle 3 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Area under the Curve (AUC) of LY2835219, Letrozole, Anastrozole, Tamoxifen, Exemestane, and Everolimus [ 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. ] [ Designated as safety issue: No ]

Estimated Enrollment: 81
Study Start Date: March 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: April 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.
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.
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.
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.
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.
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.
Drug: Exemestane
Administered orally.
Drug: Everolimus
Administered orally.

  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 breast cancer.
  • 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 either measureable disease or nonmeasureable but evaluable bone disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  • 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 endocrine 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.

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.
  • Have received prior systemic chemotherapy for metastatic disease. However, the participant may have received prior systemic chemotherapy in the neoadjuvant or adjuvant setting.
  • Have initiated bisphosphonates or approved receptor activator of nuclear factor kappa-B (RANK-L) targeted agents (for example, denosumab) ≤28 days prior to Day 1 of Cycle 1.
  • 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.
  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
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Fayetteville, Arkansas, United States, 72703
Contact: Eli Lilly         
United States, California
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
La Jolla, California, United States, 92037
Contact: Eli Lilly         
United States, Massachusetts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eli Lilly         
United States, Minnesota
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Rochester, Minnesota, United States, 55905
Contact: Eli Lilly         
United States, Nevada
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Eli Lilly         
United States, New York
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
New York, New York, United States, 10032
Contact: Eli Lilly         
United States, North Carolina
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Eli Lilly         
United States, Oklahoma
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Eli Lilly         
United States, Oregon
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Portland, Oregon, United States, 97213
Contact: Eli Lilly         
United States, Pennsylvania
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Eli Lilly         
United States, South Carolina
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Greenville, South Carolina, United States, 29605
Contact: Eli Lilly         
United States, Tennessee
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Nashville, Tennessee, United States, 37232
Contact: Eli Lilly         
United States, Texas
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Dallas, Texas, United States, 75246
Contact: Eli Lilly         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
San Antonio, Texas, United States, 78229
Contact: Eli Lilly         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
The Woodlands, Texas, United States, 77380
Contact: Eli Lilly         
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Tyler, Texas, United States, 75702
Contact: Eli Lilly         
United States, Virginia
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Recruiting
Norfolk, Virginia, United States, 23502
Contact: Eli Lilly         
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

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: August 11, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Anastrozole
Exemestane
Sirolimus
Tamoxifen
Everolimus
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents, Hormonal
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Selective Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on September 30, 2014