Study of LEE011, BYL719 and Letrozole in Advanced ER+ Breast Cancer

A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer

ClinicalTrials.gov Identifier: NCT01872260

Novartis Reference Number: CLEE011X2107

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

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.

Condition 
Breast Cancer
Phase 
Phase 1
Overall status 
Active, not recruiting
Enrollment count 
256 participants
Start date 
Oct 22, 2013
Completion date 
Dec 31, 2021
Gender 
Female
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
LEE011
LEE011 - 28 day cycles (21 days followed by a 7 day break) for Arms 1, 3. LEE011 28 days cycles (continuous) Arm 4.
Drug
Letrozole
Letrozole 2.5 mg/day
Drug
BYL719
BYL719 - 28 days cycle (continuous) for Arm 2; 3 and 4

Eligibility Criteria

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.

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 Locations

United States
University of California at San Diego, Moores Cancer Ctr Dept. of Moores Cancer Center
-
San Diego, 92103
California
United States
UCSF Medical Center
-
San Francisco, 94143
California
United States
H Lee Moffitt Cancer Center and Research Institute H. Lee Moffitt Cancer Center
-
Tampa, 33612
Florida
United States
Massachusetts General Hospital SC-5
-
Boston, 02114
Massachusetts
United States
Sarah Cannon Research Institute SCRI SC
-
Nashville, 37203
Tennessee
United States
Vanderbilt University Medical Center Vanderbilt - Thompson Ln
-
Nashville, 37232
Tennessee
United States
Texas Oncology Texas Oncology - Sammons
-
Dallas, 75246
Texas
United States
Cancer Therapy and Research Center UT Health Science Center Dept of Onc
-
San Antonio, 78229
Texas
United States
Northwest Medical Specialties Northwest Medical Specialties
-
Tacoma, 98405
Washington
United States
Australia
Novartis Investigative Site
-
Westmead, 2145
New South Wales
Australia
Novartis Investigative Site
-
Parkville, 3050
Victoria
Australia
Novartis Investigative Site
-
Nedlands, 6009
Western Australia
Australia
France
Novartis Investigative Site
-
Marseille, 13273
-
France
Novartis Investigative Site
-
Paris, 75010
-
France
Novartis Investigative Site
-
Saint Herblain cedex, 44805
-
France
Italy
Novartis Investigative Site
-
Pisa, 56126
PI
Italy
Korea, Republic of
Novartis Investigative Site
-
Seoul, 03080
-
Korea, Republic of
Spain
Novartis Investigative Site
-
Sevilla, 41013
Andalucia
Spain
Novartis Investigative Site
-
Valencia, 46010
Comunidad Valenciana
Spain
Novartis Investigative Site
-
Madrid, 28009
-
Spain
Novartis Investigative Site
-
Madrid, 28050
-
Spain
Switzerland
Novartis Investigative Site
-
Bellinzona, 6500
-
Switzerland
United Kingdom
Novartis Investigative Site
-
Glasgow, G12 0YN
Scotland
United Kingdom
Novartis Investigative Site
-
Manchester, M20 9BX
-
United Kingdom

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