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

NCT ID: NCT02088684

Last Updated: 2020-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-05-19

Study Completion Date

2018-04-17

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Cancer

Keywords

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Hormone receptor positive, HER2 negative

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes

fulvestrant

Intervention Type DRUG

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.

BKM120

Intervention Type DRUG

BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.

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.

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes

BYL719

Intervention Type DRUG

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.

fulvestrant

Intervention Type DRUG

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.

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.

Group Type EXPERIMENTAL

LEE011

Intervention Type DRUG

LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes

fulvestrant

Intervention Type DRUG

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.

Interventions

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LEE011

LEE011: supplied as capsules of dosage strength of 50 mg or 200 mg. The capsules will be differentiated through different sizes

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

BKM120

BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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University of Alabama at Birmingham/ Kirklin Clinic Dept Onc

Birmingham, Alabama, United States

Site Status

Dana Farber Cancer Institute Onc. Dept.

Boston, Massachusetts, United States

Site Status

Sarah Cannon Research Institute Onc Dept

Nashville, Tennessee, United States

Site Status

Novartis Investigative Site

Lyon, , France

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Modena, MO, Italy

Site Status

Novartis Investigative Site

Singapore, , Singapore

Site Status

Novartis Investigative Site

Seoul, Korea, South Korea

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Taipei, Taiwan ROC, Taiwan

Site Status

Novartis Investigative Site

Leicester, , United Kingdom

Site Status

Countries

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Brazil Canada Switzerland Thailand United States France Italy Singapore South Korea Spain Taiwan United Kingdom

References

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Tolaney SM, Im YH, Calvo E, Lu YS, Hamilton E, Forero-Torres A, Bachelot T, Maur M, Fasolo A, Tiedt R, Nardi L, Stammberger U, Abdelhady AM, Ruan S, Lee SC. Phase Ib Study of Ribociclib plus Fulvestrant and Ribociclib plus Fulvestrant plus PI3K Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer. Clin Cancer Res. 2021 Jan 15;27(2):418-428. doi: 10.1158/1078-0432.CCR-20-0645. Epub 2020 Sep 4.

Reference Type DERIVED
PMID: 32887722 (View on PubMed)

Related Links

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Other Identifiers

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CLEE011X2108

Identifier Type: -

Identifier Source: org_study_id