A Phase II, multi-center, open-label, neoadjuvant, randomized study ofweekly paclitaxel with or without LCL161 in patients with triple negativebreast cancer

Conditions: Women with triple negative breast cancer whose tumors are positive for a defined pattern of gene expression
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-000677-23-ES

Lead Sponsor: ovartis farmacéutica S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 100

Inclusion Criteria

- Histologically confirmed diagnosis of invasive triple negative breast cancer.
- Tumor must be positive for the LCL161 predictive gene expression profile 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.
- Absence of distant metastatic disease.
- ECOG performance status 0-1.
- Adequate bone marrow function.
- Adequate liver function and serum transaminases.
- Adequate renal function.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

- Multicentric invasive tumors; bilateral or inflammatory breast cancer, 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 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 90 days after study treatment.
- Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer that are positive for the gene expression signature.;Secondary Objective: 1. To characterize the safety and tolerability of the LCL161/paclitaxel combination compared to weekly paclitaxel alone.<br>2. To assess other indicators of disease response for the LCL161 + Paclitaxel combination compared to paclitaxel alone.<br>3. To evaluate whether combination treatment with LCL161 and<br>paclitaxel is associated with increased apoptosis compared to weekly paclitaxel alone.<br>4. To evaluate the PK of LCL161 when given in combination with<br>paclitaxel.;Primary end point(s): - Pathological complete response (pCR) rate in breast after 12 weeks of therapy in the control and experimental arms;Timepoint(s) of evaluation of this end point: 12 weeks

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: 1. 16 weeks<br>2. 12 weeks<br>3. 12 weeks<br>4. 12 weeks;Secondary end point(s): 1. Frequency of adverse events, serious adverse events and clinical<br>laboratory abnormalities<br>2.<br>- pCR rate in breast, regional nodes and axilla<br>- rates of breast conserving surgery and mastectomy<br>- clinical response<br>- disease response using RECIST 1.1 criteria<br>3. Caspase 3 activation in tumor by IHC<br>4. PK parameters including but not limited to Cmax, Tmax, and AUC last