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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02088684
First received: March 12, 2014
Last updated: July 24, 2017
Last verified: July 2017
March 12, 2014
July 24, 2017
May 19, 2014
September 1, 2017   (Final data collection date for primary outcome measure)
  • Incidence of Dose limiting toxicities (DLTs) - Phase lb only [ Time Frame: 28 days ]
    Dose limiting toxicities
  • Progression free survival (PFS) - Phase ll only [ Time Frame: 36 months ]
    Progression Free Survival per RECIST v 1.1 by local investigator assessment
Same as current
Complete list of historical versions of study NCT02088684 on ClinicalTrials.gov Archive Site
  • 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
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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
  • 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.
  • 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.
  • 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.
  • Progression Free Survival (PFS) (pahse 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.
  • 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.
Not Provided
Not Provided
 
Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
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 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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • 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.
  • Drug: BKM120
    BKM120: supplied as 10 mg or 50 mg capsules. The capsules will be differentiated through different sizes.
  • 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.
    Interventions:
    • Drug: LEE011
    • Drug: fulvestrant
    • Drug: BKM120
  • 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.
    Interventions:
    • Drug: LEE011
    • Drug: BYL719
    • Drug: fulvestrant
  • 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.
    Interventions:
    • Drug: LEE011
    • Drug: fulvestrant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
70
September 1, 2017
September 1, 2017   (Final data collection date for primary outcome measure)

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

Sexes Eligible for Study: Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France,   Italy,   Korea, Republic of,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Brazil,   Canada,   Switzerland,   Thailand
 
NCT02088684
CLEE011X2108
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Plan to Share IPD: Undecided
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

Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP