A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer

Study Identifier:
CLEE011X2107
CT.gov Identifier:
NCT01872260
EudraCT Identifier:
2013-001219-57
EU Trial (CTIS) Number:
2023-509511-84-00
Study Contact Information:
N/A
Recruitment Complete

Considering participating in a START clinical trial?

Get Started

Study Summary

To study the clinical development of the two investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha inhibitor).

To investigate the combination of LEE011 (CDK4/6i) and BYL719 (PI3K-alpha-i) with letrozole in patients with ER+/HER2- breast cancer (BC).

Phase Ib: a three-part dose escalation study

To estimate the MTD and/or RP2D for two double combinations: LEE011 with letrozole and BYL719 with letrozole followed by estimation of the MTD and/or RP2D of the triple combination of LEE011 + BYL719 with letrozole using various regimens (Arms 3 to 5 ).

Phase Ib dose expansion: To further characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the combinations. Optional crossover is allowed for patients who have progressed while on dose escalation or dose expansion with doublets treatment on Arms 1 or 2 to be treated with the triplet combination after the determination of the RP2D for Arm 3.

Potential biomarkers predictive of response were assessed by next-generation sequencing in all patients, and immunohistochemistry in available tumor samples.

Phase Ib dose escalation: To estimate the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole using various regimens (Arms 3 to 5 ).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female
    Age
    18 - 100 Years
    Study Drug
  • Drug: Experimental: LEE011 + letrozole Arm 1
    • Read More
  • Drug: ASCO 2014:
  • Drug: SABCS 2014:
  • Drug: SABCS 2015:
  • Drug: SABCS 2016:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive breast cancer
    • Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is allowed with the exception of cytotoxic therapy which is limited to one prior line administered in the advanced (metastatic or locally advanced) setting.
    • Phase Ib dose expansions Arms 1, 2 and 3
    • No prior systemic treatment in the advanced (metastatic or locally advanced) setting with the exception of treatment with letrozole for a maximum of one month prior to starting study treatment.
    • Patients who received (neo)adjuvant therapy for breast cancer are eligible. Prior therapy with letrozole or anastrozole in the (neo)adjuvant setting is permitted if the disease-free interval is greater than 12 months from the completion of treatment.
    Exclusion criteria
    • HER2-overexpression in the patient's tumor tissue
    • Patients with active CNS or other brain metastases
    • Major surgery within 2 weeks
    • Acute or chronic pancreatitis
    • Bilateral diffuse lymphangitic carcinomatosis
    • Another malignancy within 3 years
    • Receiving hormone replacement therapy that cannot be discontinued
    • Impaired cardiac function
    • Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or with fasting glucose > or = 126 mg/dL / 7.0 mmol/L or hemoglobin A1c >6.5%), history of gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
    • Other protocol-defined inclusion/exclusion criteria may apply

    Clinical Study Information for Healthcare Providers

    By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.

    View Study Information

    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers