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A Phase II Multi-center, Open-label, Neoadjuvant, Randomized Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Phase II Multi-center, Open-label, Neoadjuvant, Randomized Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer

This is a phase 2, randomized, two-arm, open-label, neoadjuvant, multicenter study in newly
diagnosed women with triple-negative breast cancer. Eligible patients will be limited to
those with clinical stages T2, N0-N2, M0.

For those patients with triple-negative disease identified on diagnostic biopsy, the
presence or absence of the gene expression signature will be determined in a molecular
pre-screening phase using the diagnostic biopsy material; patients with TNBC that are
positive and negative for the gene expression signature will be eligible for enrollment.

Following a Screening/baseline period to determine eligibility, patients will be randomized
to either paclitaxel 80 mg/m2 IV given weekly (the control arm) or paclitaxel 80 mg/m2 IV
weekly immediately followed by LCL161 1800 mg PO once weekly (the experimental arm).
Enrollment on these arms will be balanced within regions of the world and are stratified 1:1
for gene expression signature status. Treatment will be administered each week for 12 weeks
(4 cycles). The length of each treatment cycle is 21 days.

A total of 200 patients will be enrolled and treated, 100 patients in each treatment arm of
the study; each arm will contain 50 patients with gene expression signature positive disease
and 50 patients with gene expression signature negative disease.

An interim analysis is planned for this study when approximately 50 patients with gene
expression signature positive disease have been treated and have either completed the study
and have undergone surgery, or have permanently discontinued study treatment for any reason.

For all patients, a tumor biopsy will be performed approximately 24 hours after the first or
second dose of study treatment (paclitaxel or paclitaxel + LCL161) to compare the extent of
apoptosis in tumor treated with control or experimental therapy. Patients will be scheduled
for breast-conserving surgery or mastectomy 15 weeks plus a window of not more than 1 week
from the date the subject receives her first treatment (no more than 16 weeks after first
treatment). All treated patients are planned to undergo surgery. However, to evaluate the
presence of persistent disease those patients with apparent substantial residual or
progressive disease or who do not undergo surgery for any reason must have a core needle
biopsy of the primary tumor after completing study treatment. At the completion of study
treatment, patients are expected to continue post-operative treatment with a standard
anthracycline-based chemotherapy regimen such as FAC (5-FU/doxorubicin/cyclophosphamide),
FEC (5-FU/epirubicin/cyclophosphamide) or AC (doxorubicin/cyclophosphamide). The specific
regimen will be chosen by the treating physician.

Inclusion Criteria:

- Histologically confirmed diagnosis of invasive triple negative breast cancer

- Known status for the LCL161 predictive gene expression signature as determined during
molecular pre-screening

- Candidates for mastectomy or breast-conserving surgery

- Primary tumor of greater than 20 mm and less than 50 mm diameter measured by imaging

- Regional nodes N0-N2

- Absence of distant metastatic disease

- ECOG performance status 0-1

- Adequate bone marrow function

- Adequate liver function and serum transaminases

- Adequate renal function

Exclusion Criteria:

- Bilateral or inflammatory breast cancer (bilateral mammography is required during
Screening/baseline); locally recurrent breast cancer

- Patients currently receiving systemic therapy for any other malignancy, or having
received systemic therapy for a malignancy in the preceding 3 months

- Uncontrolled cardiac disease

- Patients who are currently receiving chronic treatment (>3 months) with
corticosteroids at a dose ≥ 10 mg of prednisone (or its glucocorticoid equivalent)
per day (inhaled and topical steroids are allowed), or any other chronic
immunosuppressive treatment that cannot be discontinued prior to starting study drug

- Impaired GI function that may affect the absorption of LCL161

- Pregnant or breast feeding (lactating) women

- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, unless they are using highly effective methods of contraception
during dosing and for 180 days after study treatment

- Other protocol-defined inclusion/exclusion criteria may apply

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathological complete response (pCR) rate in breast after 12 weeks of therapy

Outcome Description:

To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer, analyzed separately in the gene expression signature negative and positive groups

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals


United States: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

March 2015

Related Keywords:

  • Breast Cancer
  • Breast cancer,
  • LCL161,
  • paclitaxel,
  • neoadjuvant,
  • triple negative breast cancer
  • Breast Neoplasms



Highlands Oncology Group Dept of Highlands Oncology Grp Fayetteville, Arkansas  72703
South Texas Oncology and Hematology, PA South Texas Oncology (2) San Antonio, Texas  78258
Cancer Therapy & Research Center / UT Health Science Center InstituteForDrugDevelopment(5) San Antonio, Texas  78229
Massachusetts General Hospital Mass General 2 Boston, Massachusetts  02114
Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State Columbus, Ohio  43210
Cedars Sinai Medical Center SC Los Angeles, California  90048
Vanderbilt University Medical Center Vanderbilt - Thompson Ln Nashville, Tennessee  37232
Memorial Sloan Kettering Cancer Center Dept Onc New York, New York  10021
University of California at Los Angeles UCLA SC Los Angeles, California  90095
Stanford University Medical Center Stanford Stanford, California  94304
Yale University School of Medicine Yale Univ New Haven, Connecticut  06520
H. Lee Moffitt Cancer Center & Research Institute H. Lee Moffitt SC Tampa, Florida  33612
Baylor College of Medicine SC Dallas, Texas  75246
University of Wisconsin / Paul P. Carbone Comp Cancer Center Univ Wisc 2 Madison, Wisconsin  53792-6164