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

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.