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CompletedNCT01857193Updated Apr 13, 2021

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

A Phase 1 interventional study of ribociclib (LEE011) and Exemestane in Breast Cancer, sponsored by Novartis Pharmaceuticals. Completed at 13 sites in 5 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-04-13.

Sponsored by Novartis Pharmaceuticals · Phase 1, Interventional, and Treatment

From the registry’s dates

  • Primary completion was Mar 2018, 8 years 6 months ago, and no results have been posted to the registry.
Phase
Phase 1
Study type
Interventional
Enrollment
132
Allocation
Non-randomized
Ages
18 Years and older
Sex
Female
01

Study summary

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).

Read the detailed description

The primary purpose of the phase Ib part of this study is to determine the maximum tolerated dose(s) (MTD(s)) and/or recommended phase II dose (RP2D) of LEE011 + everolimus + exemestane in patients with ER+ Her2- advanced breast cancer. This part of the study will also assess safety, tolerability, and PK of the LEE011 + exemestane, LEE011 + everolimus + exemestane combinations.

The Dose Expansion part of the study will evaluate the triple combination of LEE011 + everolimus + exemestane and the double combination of LEE011 + exemestane for safety and tolerability.

02

Conditions studied

  • Breast Cancer

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Keywords

  • Open label
  • dose escalation
  • ER+
  • LEE011
  • CDK4/6
  • everolimus
  • advanced breast cancer
  • mTOR
  • HR positive
  • HER2 negative
03

In context

Breast Neoplasms

12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.

This study's enrollment of 132 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.

Browse Breast Neoplasms studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer
  • Histological or cytological confirmation of ER+ breast cancer in dose escalation and HR+ breast cancer in dose expansion
  • A representative tumor specimen must be available for molecular testing.
  • 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.
  • Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved

  • Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory.

    • QTcF interval at screening \< 450 msec (using Fridericia's correction).
    • Resting heart rate 50-90 bpm

Exclusion criteria

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 exemestane or mTOR inhibitors* (Note:

Patients with disease refractory to prior LEE011 are excluded for dose expansion Group 3 only).

  • History of brain or other CNS metastases.
  • Clinically significant, uncontrolled heart disease and/or recent cardiac repolarization abnormality including any of the following:
  • History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
  • Documented cardiomyopathy
  • Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Gated acquisition scan (MUGA) or echocardiogram (ECHO)
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, and etc.
  • Clinically significant cardiac arrhythmias, complete left bundle branch block, high-grade AV block
  • Systolic Blood Pressure (SBP) >160 or \<90 mmHg
  • Patients who are currently receiving treatment with agents that are known to cause QTc prolongation in humans
  • Patients who are currently receiving treatment (within 7 days prior to starting study treatment) with strong and moderate inhibitors or inducers of CYP3A4/5, substrates of CYP3A4/5 with a narrow therapeutic index or Herbal preparations/medications (Refer to Section 6.4 and Appendix 3)

Inclusion Criteria Exceptions for Phase Ib Dose Expansion patients:

Dose Expansion part of the study has 3 groups, following are the Inclusion Criteria exceptions for these 3 groups

  1. Group 1 - Patients must not have received prior treatment with any CDK4/6 inhibitors
  2. Group 2 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy
  3. Group 3 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy (except those patients who received prior LEE011 based therapy).

Other protocol-defined Inclusion/Exclusion may apply.

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
132 participants (actual)

Study arms

  • Experimental
    L-R-E arm

    Participants who took ribociclib (LEE011), everolimus (RAD001) and exemestane triple combination

    Drug: ribociclib (LEE011) · Drug: Exemestane · Drug: Everolimus (RAD001)

  • Experimental
    L-E arm

    Participants who ribociclib (LEE011) and exemestane double combination

    Drug: ribociclib (LEE011) · Drug: Exemestane

Interventions

  • Drugribociclib (LEE011)

    LEE011 is taken orally once per day for 21 days of each 28 day cycle. LEE011 comes in 50 mg and 200 mg capsules.

    Also known as: LEE011

  • DrugExemestane

    Exemestane is taken orally once per day. Exemestane comes in 25 mg tablets.

  • DrugEverolimus (RAD001)

    Everolimus is taken orally once per day. Everolimus comes in 1 mg, 2.5 mg, 5mg, and 7.5 mg tablets

    Also known as: RAD001

06

What researchers measure

Primary outcomes

  1. Dose Escalation: Incidence of Dose Limiting Toxicity (DLT)

    DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria.

    Time frame: At the end of Cycle 1 (each cycle is 28 days)

  2. Dose Expansion: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Adverse events were collected for approximately 4.5 years for dose expansion including the 30 days safety follow-up period.

    Time frame: Approximately 4.5 years after FPFV

Secondary outcomes

  1. Dose Escalation: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Adverse events were collected for approximately 6.5 years for dose escalation including the 30 days safety follow-up period.

    Time frame: Approximately 6.5 years after FPFV

  2. Dose Escalation and Expansion: Overall Response Rate (ORR)

    Overall Response Rate (ORR) is defined as the proportion of participants with a best overall response of complete response or partial response.

    Time frame: Approximately 6.5 years for Dose Escalation and 4.5 years for Dose Espansion after FPFV

  3. Dose Escalation and Expansion: Disease Control Rate (DCR)

    Disease Control Rate (DCR) is the proportion of patients with a best overall response of Complete Response or Partial Response or Stable Disease.

    Time frame: Approximately 6.5 years for Dose Escalation and 4.5 years for Dose expansion after FPFV

  4. Dose Escalation and Expansion: Clinical Benefit Rate (CBR)

    Clinical Benefit Rate (CBR) is the Complete Response, Partial Response, or Stable Disease lasting 24 weeks or longer

    Time frame: Approximately 6.5 years for Dose Escalation and 4.5 years for Dose Espansion after FPFV

  5. Dose Expansion: Duration of Response (DOR)

    Duration of Response (DOR) is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. The DOR is not applicable as none of the patients in the expansion treatment groups (triplet treatment naive, triplet treatment refractory and doublet treatment refractory) had a CR or PR

    Time frame: Approximately 4.5 years for dose expansion after FPFV

  6. Dose Expansion: Progression Free Survival (PFS)

    Progression Free Survival (PFS) is defined as the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment.

    Time frame: Approximately 4.5 years after FPFV

  7. Dose Escalation: Pharmacokinetics (PK) parameter: AUC0-24h at Day 1 of Cycle 1

    AUC0-24h is the area under the drug concentration-time curve during a dosing interval (mass x time x volume-1).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 1 Day 1

  8. Dose Escalation: Pharmacokinetics (PK) parameter: AUC0-24h at at Day 15 of Cycle 1

    AUC0-24h is the area under the drug concentration-time curve during a dosing interval (mass x time x volume-1).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 1 Day 15

  9. Dose Escalation: Pharmacokinetics (PK) parameter: Cmax at Day 1 of Cycle 1

    Cmax is the maximum observed drug concentration after drug administration (mass x volume-1).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 1 Day 1

  10. Dose Escalation: Pharmacokinetics (PK) parameter: Cmax at Day 15 of Cycle 1

    Cmax is the maximum observed drug concentration after drug administration (mass x volume-1).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 1 Day 15

  11. Dose Escalation: Pharmacokinetics (PK) parameter: Tmax at Day 1 of Cycle 1

    Tmax is the time to reach maximum plasma/blood/serum drug concentration (time).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 1 Day 1

  12. Dose Escalation: Pharmacokinetics (PK) parameter: Tmax at Day 15 of Cycle 1

    Tmax is the time to reach maximum plasma/blood/serum drug concentration (time).

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 15 Day 1

  13. Dose Escalation: Pharmacokinetics (PK) parameter: Racc at Day 15 of Cycle 1

    Racc is the accumulation ratio calculated as AUCtau,ss / AUCtau,sd

    Time frame: 6 Cycles of treatment (28 day cycles): Cycle 15 Day 1

07

Study locations

13 sites
  • Highlands Oncology Group
    Fayetteville, Arkansas 72703, United States
  • Sylvester Comprehensive Cancer Center Main Center
    Miami, Florida 33136, United States
  • Massachusetts General Hospital Onc Dept
    Boston, Massachusetts 02114, United States
  • Karmanos Cancer Institute Dept of Onc
    Detroit, Michigan 48201, United States
  • Memorial Sloan Kettering Oncology Dept.
    New York, New York 10017, United States
  • Oregon Health and Science University SC-5
    Portland, Oregon 97239, United States
  • University of Texas MD Anderson Cancer Center Onc Dept
    Houston, Texas 77030, United States
  • Northwest Medical Specialties
    Tacoma, Washington 98405, United States
  • Novartis Investigative Site
    Wilrijk, 2610, Belgium
  • Novartis Investigative Site
    Saint Herblain cedex, 44805, France
  • Novartis Investigative Site
    Hong Kong, Hong Kong
  • Novartis Investigative Site
    Barcelona, Catalunya 08035, Spain
  • Novartis Investigative Site
    Hospitalet de LLobregat, Catalunya 08907, Spain
08

References and documents

Individual participant data

Plan to share: No

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 13, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01857193
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
May 20, 2013
Start date
Sep 6, 2013
Primary completion
Mar 14, 2018
Completion
Apr 16, 2020
Last update
Apr 13, 2021

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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