A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer
18 Years
N/A
Female
Breast Cancer
Trial Information
A Phase Ib/II, Multicenter Study of the Combination of LEE011 and BYL719 With Letrozole in Adult Patients With Advanced ER+ Breast Cancer
This study will investigate the combination of LEE011 (CDK4/6i) and BYL719 (PI3K-alpha-i)
with letrozole in patients with ER+/HER2- breast cancer (BC). In the Phase Ib part of the
trial, there are three dose escalation cohorts that will enroll sequentially. Part 1 is the
escalation of the double combination LEE011 + letrozole; Part 2 is the dose escalation of
the double combination of BYL719 + letrozole; The two double combinations will be followed
by the dose escalation of the triple combination of LEE011 + BYL719 with letrozole. The
three dose escalation cohorts will enroll patients with ER+/HER2- BC with any prior
endocrine therapy in the metastatic setting and up to one prior cytotoxic regimen in the
metastatic setting. Pre- and post-treatment tumor biopsies are required in the three dose
escalation cohorts. Once the RP2D/MTD of each double regimen is identified, dose expansion
cohorts of each of these two combinations will open and will enroll in the first-line
setting to confirm the doses selected in each double combination; archival tumor tissue is
required in these cohorts, although pre- and post-biopsies in these expansion cohorts are
optional.
Once the dose is identified for the triple combination, the randomized, three-arm Phase II
portion of the study will commence enrollment. This part of the trial will enroll in the
first line setting in patients with ER+/HER2- BC and will randomize patients in a 1:1:1
ratio to either double regimen (LEE011+letrozole or BYL719 +letrozole) or the triple
combination of LEE011+BYL719 with letrozole. Archival tissue is required at study entry and
biopsies in the pre- and post-treatment setting are optional in this part of the trial.
Inclusion Criteria:
- Postmenopausal, Estrogen-receptor positive breast cancer
- Phase Ib Parts 1A and 2A Expansion and Phase II only: No prior systemic treatment in
the metastatic setting.
- Phase Ib Parts 1, 2 and 3 Dose Escalation only: Any number of prior lines of
endocrine therapy is allowed with up to one prior cytotoxic regimen in the metastatic
or locally advanced setting
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 ≥ 140 mg/dL / 7.8 mmol/L), history of gestational diabetes
mellitus or documented steroid-induced diabetes mellitus.
- Other protocol-defined inclusion/exclusion criteria may apply
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of Dose limiting toxicities (DLTs) - Phase lb only
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Novartis Pharmaceuticals
Investigator Role:
Study Director
Investigator Affiliation:
Novartis Pharmaceuticals
Authority:
United States: Food and Drug Administration
Study ID:
CLEE011X2107
NCT ID:
NCT01872260
Start Date:
July 2013
Completion Date:
April 2016
Related Keywords:
- Breast Cancer
- estrogen-receptor positive
- Breast Neoplasms
Name | Location |
|---|---|
| University of Kansas Cancer Center Univ Kansas 2 | Kansas City, Kansas 66160 |
| Cedars Sinai Medical Center Cedars 2 | Los Angeles, California 90048 |
| Massachusetts General Hospital SC-5 | Boston, Massachusetts 02114 |
| Highlands Oncology Group Oncology Group | Fayetteville, Arkansas 72703 |
| University of California at San Diego, Moores Cancer Ctr Dept. of Moores Cancer Center | San Diego, California 92103 |
| Indiana University Health Goshen Center for Cancer Dept of Onc | Indianapolis, Indiana 46202 |
| University of Cincinnati Dept of Oncology | Cincinnati, Ohio 45267 |
| Sanford Research Dept of Oncology | Sioux Falls, South Dakota 57104 |
| Northwest Medical Specialties Dept of Onc | Tacoma, Washington 98405 |
