Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer

Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Breast: Metastatic
NCT ID: NCT01857193 (View complete trial on
DFCI Protocol ID: 13-283


Dose Escalation part of the study: To estimate the MTD(s) and/ or RP2D of LEE011 in combination with everolimus + exemestane, and LEE011 in combination with exemestane, and to characterize the safety and tolerability of the combinations of everolimus + exemestane + LEE011 and LEE011 + exemestane in patients with ER+ HER2- advanced breast cancer Dose Expansion part of the study: To characterize the safety and tolerability of the triplet combination of LEE011 + everolimus + exemestane in patients naïve or refractory to CDK4/6 inhibitor based therapy, and the safety and tolerability of the doublet combination of LEE011 + exemestane in patients refractory to CDK4/6 inhibitor based therapy (except patients treated with prior LEE011 are not allowed in Group 3).


Conducting Institutions:
Massachusetts General Hospital

Overall PI:
Aditya Bardia MD, MPH, Massachusetts General Hospital

Site-responsible Investigators:

Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy - Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer - A representative tumor specimen must be available for molecular testing. An archival tumor sample may be submitted; if one is not available, a newly obtained tumor specimen must be submitted instead - Postmenopausal women. Postmenopausal status is defined either by: - Age ≥ 18 with prior bilateral oophorectomy - Age ≥ 60 years - Age <60 years with amenorrhea for at least 12 months and both follicle-stimulating hormone (FSH) and estradiol levels are in postmenopausal range (according to the local laboratory) - Recurrence while on, or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or - Progression while on, or within one month of end of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer. - Patients must have: - Measurable disease*: At least one lesion that can be accurately measured in at least one dimension ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI or - Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above. - ECOG Performance Status 0-1. - Exception for Phase Ib patients: measurable disease is not required Exclusion Criteria: - Her2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive). - Patients who received more than one chemotherapy line for advanced breast cancer. - Previous treatment with CDK4/6 inhibitors, exemestane or mTOR inhibitors*. - History of active or symptomatic brain or other CNS metastases. - Impaired cardiac function or clinically significant cardiac diseases, including any of the following: - Left ventricular ejection fraction (LVEF) < 45% or less than the institution lower limit of normal as determined by multiple gated acquisition scan (MUGA) or echocardiogram (ECHO) - Congenital long QT syndrome or family history of unexpected sudden cardiac death - QT corrected with Fredericia's (QTcF) >470 ms for females on screening ECG - Any other clinically significant heart disease such as angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, Right bundle branch block with left anterior hemiblock (bifascicular block), acute myocardial infarction or any heart disease that requires the use of a cardiac pacemaker or implantable cardioverter defibrillator ≤ 3 months prior to starting study drug. - Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans. - Patients who are currently receiving treatment (within five days prior to randomization) with agents that are metabolized predominantly through CYP3A4 and that have a narrow therapeutic window. Agents that are known strong inducers or inhibitors CYP3A4 are prohibited (Refer to Appendix 4) * Exceptions for Phase Ib patients: 1. Patients who received more than two prior lines of chemotherapy are eligible 2. Patients who received CDK4/6 inhibitors, exemestane or mTOR inhibitors are eligible
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