Clinical trial NCT01617668
Conditions: Breast Cancer
Keywords: Breast cancer, LCL161, paclitaxel, neoadjuvant, triple negative breast cancer
Sponsor: Novartis Pharmaceuticals
Start date: 2012-08-01; Completion date: 2014-09-01
Enrollment: 209 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer whose tumors are positive for a defined pattern of gene expression

Detailed description:
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.

Arms: arm 1: Patients randomized to the experimental arm received paclitaxel 80 mg/m2 weekly + LECL161 1800 mg once weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm. arm 2: Patients randomized to the control arm received paclitaxel 80 mg/m2 weekly for 12 weeks. Equal numbers of patients with gene expression signature positive and negative disease were included in each treatment arm.
Interventions: intervention 1: LCL161 intervention 2: paclitaxel
Intervention descriptions: intervention 1: LCL161 was available as 300 mg, tablets, which was supplied in child-resistant bottles. intervention 2: Commercially available paclitaxel was sourced locally by each study site. Generic paclitaxel could be used for study treatment.

iv 80mg/m2

Protocol documents: