NCT02088684

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P50-P75 for phase_1 breast-cancer

Timeline
Completed

Started May 2014

Typical duration for phase_1 breast-cancer

Geographic Reach
8 countries

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 12, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

March 17, 2014

Completed
2 months until next milestone

Study Start

First participant enrolled

May 19, 2014

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 17, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 17, 2018

Completed
Last Updated

December 17, 2020

Status Verified

April 1, 2019

Enrollment Period

3.9 years

First QC Date

March 12, 2014

Last Update Submit

December 16, 2020

Conditions

Breast Cancer

Keywords

Hormone receptor positive, HER2 negative

Outcome Measures

Primary Outcomes (2)

  • Incidence of Dose limiting toxicities (DLTs) - Phase lb only

    Dose limiting toxicities

    28 days

  • Progression free survival (PFS) - Phase ll only

    Progression Free Survival per RECIST v 1.1 by local investigator assessment

    36 months

Secondary Outcomes (6)

  • Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant

    36 months

  • Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.

    36 months

  • Overall Response Rate (ORR)

    36 months

  • Duration of Response (DOR)

    36 months

  • Progression Free Survival (PFS) (phase l only)

    36 months

  • +1 more secondary outcomes

Study Arms (3)

LEE011 + BKM120 + fulvestrant

EXPERIMENTAL

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: LEE011Drug: fulvestrantDrug: BKM120

LEE011 + BYL719 + fulvestrant

EXPERIMENTAL

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: LEE011Drug: BYL719Drug: fulvestrant

LEE011 + fulvestrant

EXPERIMENTAL

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: LEE011Drug: fulvestrant

Interventions

LEE011DRUG

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

LEE011 + BKM120 + fulvestrantLEE011 + BYL719 + fulvestrantLEE011 + fulvestrant
BYL719DRUG

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.

LEE011 + BYL719 + fulvestrant
fulvestrantDRUG

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 + BKM120 + fulvestrantLEE011 + BYL719 + fulvestrantLEE011 + fulvestrant
BKM120DRUG

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

LEE011 + BKM120 + fulvestrant

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of Alabama at Birmingham/ Kirklin Clinic Dept Onc

Birmingham, Alabama, 35294-0006, United States

Location

Dana Farber Cancer Institute Onc. Dept.

Boston, Massachusetts, 02215, United States

Location

Sarah Cannon Research Institute Onc Dept

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Modena, MO, 41124, Italy

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Seoul, Korea, 06351, South Korea

Location

Novartis Investigative Site

Madrid, 28050, Spain

Location

Novartis Investigative Site

Taipei, Taiwan ROC, 10041, Taiwan

Location

Novartis Investigative Site

Leicester, LE1 5WW, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 32887722DERIVED

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclibAlpelisibFulvestrantNVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

EstradiolEstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 12, 2014

First Posted

March 17, 2014

Study Start

May 19, 2014

Primary Completion

April 17, 2018

Study Completion

April 17, 2018

Last Updated

December 17, 2020

Record last verified: 2019-04

Locations

TW(1)GB(1)IT(2)ES(1)KR(1)US(3)FR(1)SG(1)