A Study of LY2835219 Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer (MONARCH 2)

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:
NCT02107703
First received: April 4, 2014
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breast cancer receiving either LY2835219+fulvestrant or fulvestrant alone. The study will last about 9 months for each participant.


Condition Intervention Phase
Breast Neoplasms
Drug: LY2835219
Drug: Fulvestrant
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Fulvestrant With or Without LY2835219, a CDK4/6 Inhibitor, for Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: Baseline up to Approximately 80 Months ] [ Designated as safety issue: No ]
  • Objective Response Rate [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Duration of Response (DoR) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Disease Control Rate (DCR) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Clinical Benefit Rate (CBR) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Pain and Symptom Burden Assessment Using the Brief Pain Inventory (BPI) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]
  • Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of LY2835219, Its Metabolites, and Fulvestrant [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Time to First Skeletal-Related Event (SRE) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]
  • Change from Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]
  • Change from Baseline in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]
  • Change from Baseline in Quality of Life Using the EORTC QLQ-BR23 (breast) Questionnaire [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]

Estimated Enrollment: 550
Study Start Date: July 2014
Estimated Study Completion Date: February 2020
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2835219 + Fulvestrant
200 milligrams (mg) LY2835219 given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Drug: LY2835219
Other Name: Administered Orally
Drug: Fulvestrant
Other Name: Administered IM
Placebo Comparator: Placebo + Fulvestrant
Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.
Drug: Fulvestrant
Other Name: Administered IM
Drug: Placebo
Other Name: 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 HR+, HER2- breast cancer
  • Have either locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:

    • relapsed with radiologic evidence of progression on neoadjuvant or adjuvant endocrine therapy
    • relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy
    • relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after no more than first-line endocrine therapy (with either an antiestrogen or an aromatase inhibitor) for metastatic disease
    • presented de novo with locally advanced or metastatic disease and not received any prior endocrine therapy
    • presented de novo with locally advanced or metastatic disease and then relapsed with radiologic evidence of progression after no more than first-line endocrine therapy (with either an antiestrogen or an aromatase inhibitor)
  • Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin
  • Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of LY2835219 if postmenopausal status is due to ovarian suppression with a GnRH agonist
  • Have either measurable disease or nonmeasurable bone only disease
  • Have a performance status ≤1 on the ECOG scale
  • Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, 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

  • Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study
  • Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease
  • Have clinical evidence or history of central nervous system metastasis
  • Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor
  • Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively
  • Have received recent (within 28 days prior to randomization) yellow fever vaccination
  • Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)
  • Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest
  • Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years
  • Have received an autologous or allogeneic stem-cell transplant
  • Have active bacterial or fungal infection, or detectable viral infection
  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: NCT02107703

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

  Show 123 Study Locations
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: NCT02107703     History of Changes
Other Study ID Numbers: 15362, I3Y-MC-JPBL, 2013-004728-13
Study First Received: April 4, 2014
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Russia: Ministry of Health of the Russian Federation
Japan: Ministry of Health, Labor and Welfare
Korea: Ministry of Food and Drug Safety
Taiwan: Ministry of Health and Welfare
Denmark: Danish Health and Medicines Authority
Finland: Finnish Medicines Agency
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Poland: The Central Register of Clinical Trials
Romania: National Authority for Scientific Research
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Mexico: Ministry of Health
Canada: Health Canada

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Fulvestrant
Estradiol
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Estrogens
Hormones

ClinicalTrials.gov processed this record on August 28, 2014