Clinical trial NCT02154776: Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole in HR+, HER2-negative Post-menopausal Women With Advanced Breast Cancer.
Official title: A Phase 1 Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole for the Treatment of HR+, HER2-negative Post-menopausal Women With Locally Advanced or Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced or Metastatic Breast Cancer
Keywords: LEE011,
buparlisib,
letrozole,
HR +,
HER2 - negative,
post-menopausal,
breast cancer,
CDK 4/6,
PI3K,
MTD
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-06-03
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: This is a multi-center, open-label, non-randomized, phase I study


Eligibility criteria: Inclusion Criteria:

1. Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
2. Patient is postmenopausal.
3. Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase.
4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
5. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing.
6. Patient must have either:

   * Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion

Exclusion Criteria:

1. Patient who received any CDK4/6 or PI3K inhibitor.
2. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:

   * History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry
   * History of documented congestive heart failure (New York Heart Association functional classification III-IV)
   * Documented cardiomyopathy
   * Patient has a Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
   * History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months.
   * On screening, any of the following cardiac parameters: bradycardia (heart rate \< 50 at rest), tachycardia (heart rate \> 90 at rest), PR interval \> 220 msec, QRS interval \>109 msec, or QTcF \>450 msec.

   Systolic blood pressure \>160 or \<90 mmHg
3. Patient is currently receiving any of the following medications:

   * That are known strong inducers or inhibitors of CYP3A4.
   * That have a known risk to prolong the QT interval or induce Torsades de Pointes.
   * That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.
4. Certain scores on an anxiety and depression mood questionnaires

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 28 days
measure: Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
timeFrame: approximately 25 months
Secondary outcomes:
measure: Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole
timeFrame: approximately 25 months
measure: Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
timeFrame: approximately 25 months
measure: Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
timeFrame: approximately 25 months
measure: Disease control rate
timeFrame: approximately 25 months
measure: PFS (progression free survival)
timeFrame: approximately 25 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California at Los Angeles UCLA SC
state: California
city: Lafayette
country: United States
facility: Horizon Oncology Center SC
state: Indiana
city: Charleston
country: United States
facility: Medical University of South Carolina SC
state: South Carolina
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics SC
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah / Huntsman Cancer Institute SC-3
state: Utah
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: