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Breast CancerPhase 1NCT02088684

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

A Phase 1 study testing LEE011, BYL719 and fulvestrant in people with Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
LEE011, BYL719 and fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
11 sitesin 8 countries
Study dates
19 May 2014to 17 Apr 2018
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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

Trial locations and contacts

11 sites in 8 countries.

11 sites in 8 countries

United States3 sites

  • University of Alabama at Birmingham/ Kirklin Clinic Dept Onc

    Birmingham, Alabama, 35294-0006

  • Dana Farber Cancer Institute Onc. Dept.

    Boston, Massachusetts, 02215

  • Sarah Cannon Research Institute Onc Dept

    Nashville, Tennessee, 37203

Other trials in United States

Italy2 sites

  • Novartis Investigative Site

    Milan, MI, 20132

  • Novartis Investigative Site

    Modena, MO, 41124

Other trials in Italy

France1 site

  • Novartis Investigative Site

    Lyon, 69373

Other trials in France

Singapore1 site

  • Novartis Investigative Site

    Singapore, 119228

Other trials in Singapore

South Korea1 site

  • Novartis Investigative Site

    Seoul, Korea, 06351

Other trials in South Korea

Spain1 site

  • Novartis Investigative Site

    Madrid, 28050

Other trials in Spain

Taiwan1 site

  • Novartis Investigative Site

    Taipei, Taiwan ROC, 10041

Other trials in Taiwan

United Kingdom1 site

  • Novartis Investigative Site

    Leicester, LE1 5WW

Other trials in United Kingdom

About this study

Official title: 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.

Read more

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.

Read the 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.

Conditions
Breast Cancer
Being tested
LEE011, BYL719, fulvestrant, BKM120
Keywords
Hormone receptor positive, HER2 negative
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LEE011Drug

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

  • 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.

  • 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.

  • BKM120Drug

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

Study groups in NCT02088684
Study groupRoleWhat they receive
LEE011 + BKM120 + fulvestrantExperimentalLEE011 - 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.
Receives: Drug: LEE011; Drug: fulvestrant; Drug: BKM120
LEE011 + BYL719 + fulvestrantExperimentalLEE011 - 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.
Receives: Drug: LEE011; Drug: BYL719; Drug: fulvestrant
LEE011 + fulvestrantExperimentalLEE011 - 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.
Receives: Drug: LEE011; Drug: fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Dose limiting toxicities

    Measured: 28 days

  2. Progression free survival (PFS) - Phase ll only

    Progression Free Survival per RECIST v 1.1 by local investigator assessment

    Measured: 36 months

Secondary outcomes (6)

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

    Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity

    Measured: 36 months

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

    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.

    Measured: 36 months

  3. Overall Response Rate (ORR)

    ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

    Measured: 36 months

  4. Duration of Response (DOR)

    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.

    Measured: 36 months

  5. Progression Free Survival (PFS) (phase l only)

    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.

    Measured: 36 months

  6. Overall Survival (OS) - Phase II only

    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.

    Measured: 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2014 (estimated)
  2. Study start19 May 2014
  3. Primary completion17 Apr 2018
  4. Study completion17 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02088684
Sponsor's protocol ID
CLEE011X2108
Status last verified
Apr 2019
First submitted
12 Mar 2014
Last updated
17 Dec 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: 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

Publications

  • 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.

    PubMed 32887722

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LEE011, BYL719 and fulvestrant in people with Breast Cancer, run by Novartis Pharmaceuticals at 11 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Italy, France, Singapore, South Korea and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose limiting toxicities (DLTs) - Phase lb only (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02088684, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.

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