Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer

December 16, 2020 updated by: Novartis Pharmaceuticals

A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer

The purpose of this trial is to explore the clinical utility of the three investigational agents in HR+, HER2- breast cancer. LEE011 (CDK4/6 inhibitor), BKM120 (PI3K-pan class I-inhibitor) and BYL719 (PI3K-alpha specific class I inhibitor) in combination with fulvestrant.

This is a multi-center, open-label Phase Ib/II study. The Phase Ib portion of the study is a dose escalation to estimate the MTD and/or RP2D for three regimens: LEE011 with fulvestrant; LEE011 and BKM120 with fulvestrant; LEE011and BYL719 with fulvestrant.

The Phase II portion of the study was planned to be a randomized study to assess the anti-tumor activity as well as safety and tolerability of LEE011 with fulvestrant to LEE011 and BKM120 with fulvestrant, and LEE011 and BYL719 with fulvestrant in patients with ER+/HER2- locally advanced or metastatic breast cancer.

Approximately 216 adult women with ER+/HER2- locally advanced or metastatic breast cancer were planned to be enrolled.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

On 31-May-2016 Novartis's made the decision decision to not open the Phase II portion of the study, for business reasons. Sufficient data had already been collected and no additional data for the triplet combinations was needed. As a result, the Phase II portion of the trial was not opened.

Study Type

Interventional

Enrollment (Actual)

70

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon Cedex, France, 69373
        • Novartis Investigative Site
  • Italy
    • MI
      • Milano, MI, Italy, 20132
        • Novartis Investigative Site
    • MO
      • Modena, MO, Italy, 41124
        • Novartis Investigative Site
  • Korea, Republic of
    • Korea
      • Seoul, Korea, Korea, Republic of, 06351
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28050
        • Novartis Investigative Site
  • Taiwan
    • Taiwan ROC
      • Taipei, Taiwan ROC, Taiwan, 10041
        • Novartis Investigative Site
  • United Kingdom
      • Leicester, United Kingdom, LE1 5WW
        • Novartis Investigative Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-0006
        • University of Alabama at Birmingham/ Kirklin Clinic Dept Onc
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute Onc. Dept.
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute Onc Dept

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
  • Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)
  • Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)

Exclusion Criteria:

  • HER2-overexpression in the patient's tumor tissue
  • Inadequate bone marrow function or evidence of end-organ damage
  • Severe or uncontrolled medical issues
  • Diabetes mellitus

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: LEE011 + BKM120 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
Drug: LEE011
LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes
Drug: fulvestrant
Fulvestrant will be supplied according to local practice and regulation. Fulvestrant is a commercially available product, comes in 500 mg dose and is an injection for intramuscular (i.m.) administration.
Drug: BKM120
BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.
Experimental: LEE011 + BYL719 + fulvestrant
LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
Drug: LEE011
LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes
Drug: fulvestrant
Fulvestrant will be supplied according to local practice and regulation. Fulvestrant is a commercially available product, comes in 500 mg dose and is an injection for intramuscular (i.m.) administration.
Drug: BYL719
BYL719: supplied as tablets of dosage strength of 10 mg, 50 mg or 200 mg. Tablets will be differentiated through different sizes and/or colors.
Experimental: LEE011 + fulvestrant
LEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
Drug: LEE011
LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes
Drug: fulvestrant
Fulvestrant will be supplied according to local practice and regulation. Fulvestrant is a commercially available product, comes in 500 mg dose and is an injection for intramuscular (i.m.) administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Time Frame: 28 days
Dose limiting toxicities
28 days
Progression free survival (PFS) - Phase ll only
Time Frame: 36 months
Progression Free Survival per RECIST v 1.1 by local investigator assessment
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant
Time Frame: 36 months
Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity
36 months
Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.
Time Frame: 36 months
To characterize the PK profiles of LEE011, BKM120, BYL719, and fulvestrant when used in combination as well as to evaluate any other clinically significant metabolites that may be identified. PK parameters for LEE011, BKM120 and BYL719, including but not limited to Cmax, Cmin, Tmax, AUCtau, accumulation ratio (Racc),and Ctrough values for fulvestrant.
36 months
Overall Response Rate (ORR)
Time Frame: 36 months
ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
36 months
Duration of Response (DOR)
Time Frame: 36 months
Duration of Response 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.
36 months
Progression Free Survival (PFS) (phase l only)
Time Frame: 36 months
PFS is 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.
36 months
Overall Survival (OS) - Phase II only
Time Frame: 36 months
OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.
36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 19, 2014

Primary Completion (Actual)

April 17, 2018

Study Completion (Actual)

April 17, 2018

Study Registration Dates

First Submitted

March 12, 2014

First Submitted That Met QC Criteria

March 13, 2014

First Posted (Estimate)

March 17, 2014

Study Record Updates

Last Update Posted (Actual)

December 17, 2020

Last Update Submitted That Met QC Criteria

December 16, 2020

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLEE011X2108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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