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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01872260




Registration number
NCT01872260
Ethics application status
Date submitted
30/05/2013
Date registered
7/06/2013

Titles & IDs
Public title
Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer
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
Secondary ID [1] 0 0
2013-001219-57
Secondary ID [2] 0 0
CLEE011X2107
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Assessment method [1] 0 0
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Safety and tolerability
Assessment method [2] 0 0
Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity.
Timepoint [2] 0 0
Average 18 months
Primary outcome [3] 0 0
PK profiles of LEE011 and letrozole
Assessment method [3] 0 0
To characterize PK profiles of LEE011 and Letrozole.
Timepoint [3] 0 0
18 months
Secondary outcome [1] 0 0
Safety and tolerability of LEE011 in combination with letrozole, BYL719 in combination with letrozole, and the triple combination of LEE011 +BYL719 with letrozole
Assessment method [1] 0 0
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
Timepoint [1] 0 0
Average 24 months
Secondary outcome [2] 0 0
Plasma concentration-time profiles of LEE011, BYL719 and letrozole
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
Average 24 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR)
Assessment method [3] 0 0
ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
Timepoint [3] 0 0
Average 24 months
Secondary outcome [4] 0 0
Duration of Response (DOR)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Average 24 months
Secondary outcome [5] 0 0
Progression Free Survival (PFS)
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Average 24 months
Secondary outcome [6] 0 0
Pharmacokinetics (PK) parameters, including but not limited to AUCtau, Cmin, Cmax, Tmax, accumulation ratio (Racc)
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Average 24 months
Secondary outcome [7] 0 0
Safety and tolerability of the triple combination of LEE011 +BYL719 with letrozole in patients previously treated with either doublet
Assessment method [7] 0 0
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
Timepoint [7] 0 0
Average 24 months

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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Females
Can healthy volunteers participate?
No
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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
Accrual to date
Final
256
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
France
State/province [7] 0 0
Marseille
Country [8] 0 0
France
State/province [8] 0 0
Paris 10
Country [9] 0 0
France
State/province [9] 0 0
Saint Herblain
Country [10] 0 0
Italy
State/province [10] 0 0
PI
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Seoul
Country [12] 0 0
Spain
State/province [12] 0 0
Andalucia
Country [13] 0 0
Spain
State/province [13] 0 0
Comunidad Valenciana
Country [14] 0 0
Spain
State/province [14] 0 0
Madrid
Country [15] 0 0
Switzerland
State/province [15] 0 0
Bellinzona
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Glasgow
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT01872260