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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02088684
First received: March 12, 2014
Last updated: April 7, 2016
Last verified: April 2016
  Purpose

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 will 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 will be enrolled.


Condition Intervention Phase
Breast Cancer
Drug: LEE011
Drug: BYL719
Drug: fulvestrant
Drug: BKM120
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Incidence of Dose limiting toxicities (DLTs) - Phase lb only [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Dose limiting toxicities

  • Progression free survival (PFS) - Phase ll only [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Progression Free Survival per RECIST v 1.1 by local investigator assessment


Secondary Outcome Measures:
  • Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity

  • Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.

  • Overall Response Rate (ORR) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

  • Duration of Response (DOR) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.

  • Progression Free Survival (PFS) (phase l only) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.

  • Overall Survival (OS) - Phase II only [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 216
Study Start Date: May 2014
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: 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.
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02088684

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

Locations
United States, Alabama
University of Alabama at Birmingham/ Kirklin Clinic Dept Onc Recruiting
Birmingham, Alabama, United States, 35294-0006
Contact: Carla Perna    205-934-0337    cperna@uab.edu   
Principal Investigator: Andres Forero-Torres         
United States, Massachusetts
Dana Farber Cancer Institute Onc. Dept. Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nicole Ryabin    617-632-6767    nryabin@partners.org   
Principal Investigator: Sara Tolaney         
United States, Tennessee
Sarah Cannon Research Institute Onc Dept Recruiting
Nashville, Tennessee, United States, 37203
Contact: Lorie Patterson    615-329-7432    Lorie.Patterson@scresearch.net   
Principal Investigator: Erika P. Hamilton         
France
Novartis Investigative Site Recruiting
Lyon Cedex, France, 69373
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20132
Novartis Investigative Site Recruiting
Modena, MO, Italy, 41100
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Korea, Republic of, 06351
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Spain
Novartis Investigative Site Recruiting
Madrid, Spain, 28050
Taiwan
Novartis Investigative Site Recruiting
Taipei, Taiwan ROC, Taiwan, 100
United Kingdom
Novartis Investigative Site Recruiting
Leicester, United Kingdom, LE1 5WW
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02088684     History of Changes
Other Study ID Numbers: CLEE011X2108 
Study First Received: March 12, 2014
Last Updated: April 7, 2016
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Singapore: Health Sciences Authority
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: National Institute of Health
South Korea: Korea Food and Drug Administration (KFDA)
Taiwan: Center for Drug Evaluation
Spain: Comité Ético de Investigación Clínica

Keywords provided by Novartis:
Hormone receptor positive, HER2 negative

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Estradiol
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Estrogens
Hormones

ClinicalTrials.gov processed this record on August 28, 2016