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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01872260
Registration number
NCT01872260
Ethics application status
Date submitted
30/05/2013
Date registered
7/06/2013
Date last updated
7/05/2024
Titles & IDs
Public title
Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
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Scientific title
A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer
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Secondary ID [1]
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2013-001219-57
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Secondary ID [2]
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CLEE011X2107
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Breast Cancer
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Condition category
Condition code
Cancer
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Breast
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LEE011
Treatment: Drugs - Letrozole
Treatment: Drugs - BYL719
Experimental: LEE011 + letrozole Arm 1 - LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating), letrozole - 2.5 mg/day
Experimental: BYL719 + letrozole Arm 2 - BYL719 - daily (dose escalating) letrozole - 2.5 mg/day
Experimental: LEE011 + BYL719 + letrozole Arm 3 - LEE011 - 28 day cycles (21 days followed by a 7 day break -dose escalating), BYL719 - daily (dose escalating), letrozole 2.5 mg/day
Experimental: LEE011+ BYL719+letrozole Arm 4 - LEE011-daily (dose escalating), BYL719 -daily (dose escalating), letrozole 2.5 mg/day
Treatment: Drugs: LEE011
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4.
Treatment: Drugs: Letrozole
Letrozole 2.5 mg/day
Treatment: Drugs: BYL719
BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Incidence of Dose limiting toxicities (DLTs) - Phase lb only
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Assessment method [1]
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Timepoint [1]
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28 days
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Primary outcome [2]
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Safety and tolerability
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Assessment method [2]
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Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
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Timepoint [2]
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Average 18 months
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Primary outcome [3]
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PK profiles of LEE011 and letrozole
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Assessment method [3]
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To characterize PK profiles of LEE011 and Letrozole.
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Timepoint [3]
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18 months
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Secondary outcome [1]
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Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole
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Assessment method [1]
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Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
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Timepoint [1]
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Average 24 months
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Secondary outcome [2]
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Plasma concentration-time profiles of LEE011, BYL719 and letrozole
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Assessment method [2]
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To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified.
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Timepoint [2]
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Average 24 months
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Secondary outcome [3]
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Overall Response Rate (ORR)
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Assessment method [3]
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ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
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Timepoint [3]
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Average 24 months
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Secondary outcome [4]
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Duration of Response (DOR)
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Assessment method [4]
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DOR 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.
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Timepoint [4]
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Average 24 months
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Secondary outcome [5]
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Progression Free Survival (PFS)
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Assessment method [5]
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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.
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Timepoint [5]
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Average 24 months
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Secondary outcome [6]
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Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)
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Assessment method [6]
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To characterize the PK profiles of LEE011, BYL719, and letrozole when used in combination as well as to evaluate any other clinically significant metabolites that may be identified.
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Timepoint [6]
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Average 24 months
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Secondary outcome [7]
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Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet
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Assessment method [7]
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Safety and tolerability will be determined by type, frequency and severity of adverse events and laboratory abnormalities per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
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Timepoint [7]
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Average 24 months
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Eligibility
Key inclusion criteria
- Postmenopausal, Estrogen-receptor positive and/or Progesterone-receptor positive
breast cancer
- Phase Ib dose escalation only: Any number of prior lines of endocrine therapy is
allowed with the exception of cytotoxic therapy which is limited to one prior line
administered in the advanced (metastatic or locally advanced) setting.
- Phase Ib dose expansions Arms 1, 2 and 3
- No prior systemic treatment in the advanced (metastatic or locally advanced) setting
with the exception of treatment with letrozole for a maximum of one month prior to
starting study treatment.
- Patients who received (neo)adjuvant therapy for breast cancer are eligible. Prior
therapy with letrozole or anastrozole in the (neo)adjuvant setting is permitted if the
disease-free interval is greater than 12 months from the completion of treatment.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- HER2-overexpression in the patient's tumor tissue
- Patients with active CNS or other brain metastases
- Major surgery within 2 weeks
- Acute or chronic pancreatitis
- Bilateral diffuse lymphangitic carcinomatosis
- Another malignancy within 3 years
- Receiving hormone replacement therapy that cannot be discontinued
- Impaired cardiac function
- Patients with clinically manifest diabetes mellitus (treated and/or clinical signs or
with fasting glucose = 126 mg/dL / 7.0 mmol/L or hemoglobin A1c >6.5%), history of
gestational diabetes mellitus or documented steroid-induced diabetes mellitus.
- Other protocol-defined inclusion/exclusion criteria may apply
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
22/10/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
31/12/2024
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Actual
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Sample size
Target
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Accrual to date
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Final
255
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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Novartis Investigative Site - Westmead
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Recruitment hospital [2]
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Novartis Investigative Site - Parkville
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Recruitment hospital [3]
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Novartis Investigative Site - Nedlands
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Florida
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United States of America
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Massachusetts
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United States of America
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Tennessee
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Country [5]
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United States of America
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Texas
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Country [6]
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United States of America
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State/province [6]
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Washington
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Country [7]
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France
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State/province [7]
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Marseille
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Country [8]
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France
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State/province [8]
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Paris 10
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Country [9]
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France
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State/province [9]
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Saint Herblain
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Italy
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State/province [10]
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PI
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Korea, Republic of
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State/province [11]
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Seoul
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Spain
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State/province [12]
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Andalucia
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Country [13]
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Spain
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State/province [13]
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Comunidad Valenciana
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Spain
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State/province [14]
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Madrid
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Switzerland
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State/province [15]
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Bellinzona
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United Kingdom
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State/province [16]
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Glasgow
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Country [17]
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United Kingdom
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State/province [17]
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this trial is to inform the future clinical development of the two
investigational agents in ER+ breast cancer, LEE011 (CDK4/6 inhibitor) and BYL719 (PI3K-alpha
inhibitor).
This is a multi-center, open-label Phase Ib study. The Phase Ib dose escalation will estimate
the MTD and/or RP2D for three regimens: two double combinations, LEE011 with letrozole and
BYL719 with letrozole, followed by triple combinations of LEE011 + BYL719 with letrozole
(Arms 3 and 4).
The Phase Ib dose escalation part will be followed by Phase Ib dose expansions to further
characterize the safety, tolerability, PK and preliminary clinical anti-tumor activity of the
combinations. Optional crossover for patients who have progressed while on dose escalation or
dose expansion with doublet treatment on Arms 1 or 2 to be treated with the triplet
combination (Arm 3) after the determination of the RP2D for Arm 3; is no longer permitted
after protocol amendment 6.
Approximately 270 adult women with ER+/HER2- locally advanced or metastatic breast cancer
will be enrolled.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01872260
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01872260
Download to PDF