A Phase II Multi-center, Open-label, Neoadjuvant, Randomized Study of Weekly Paclitaxel With or Without LCL161 in Patients With Triple Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 209
- 试验地点
- 14
- 主要终点
- Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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 or equal to 50 mm diameter measured by imaging (previous Amendment #3 was tumor size greater than 10 mm)
- •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
排除标准
- •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
研究组 & 干预措施
Paclitaxel with LCL161
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.
干预措施: LCL161 (Drug)
Paclitaxel with LCL161
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.
干预措施: paclitaxel (Drug)
Paclitaxel without LCL161
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.
干预措施: paclitaxel (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate in Breast After 12 Weeks of Therapy
时间窗: 12 weeks
pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on Bayesian design using a binomial distribution for the data with a beta prior. The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). Median values are posterior medians of pCR rate for each group.
Number of Participants With Pathological Complete Response (pCR) in Breast After 12 Weeks of Therapy
时间窗: 12 weeks
To assess the number of patients who experienced a pathological response in breast.
Difference in pCR Rates Between Treatment Arms
时间窗: 12 weeks
pCR rate was defined as histopathologically confirmed absence of invasive disease in the breast. To assess whether adding LCL161 to weekly paclitaxel enhances the efficacy of paclitaxel in women with triple negative breast cancer. Analyses were performed separately in the gene expression signature negative and positive groups. This analysis was based on the posterior distribution of the difference in pCR rates between the experimental and control arms of the study, within each gene expression signature group.The measurement type used for this analysis is posterior median and the method of dispersion is Credible Interval (Crl) and not Confidence Interval (CI). 95% Confidence interval is actually 95% credible interval.
次要结局
- Posterior Distribution of Difference of pCR Rates After Treatment With LCL161 + Paclitaxel Between Patients With Gene Expression Positive and Negative Tumors(12 weeks)
- Posterior Distribution of Difference in pCR Rates After Treatment With Paclitaxel Only Between Gene Expression Positive and Negative Tumors(12 weeks)
- pCR Rate in Breast After 12 Weeks of Therapy With Single Agent LCL161 and LCL161 + Paclitaxel, Regardless of Gene Signature Status(12 weeks)
- pCR Rate in Breast, Regional Nodes and Axilla(12 weeks)
- Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS2(Baseline, Post-baeline at Cycle 1, Day 2 or Cycle 1, Day 9)
- Pharmacokinetics (PK) Parameters of LCL161 Only for Cmax(cycle 1 day 1, cycle 4 day 15)
- Pharmacokinetics (PK) Parameters of LCL161 Only for Tmax(cycle 1 day 1, cycle 4 day 15)
- Pharmacokinetics (PK) Parameters of LCL161 Only for AUClast(cycle 1 day 1, cycle 4 day 15)
- Rates of Breast Conserving Surgery and Mastectomy - Assessed by Percentage of Patients Who Underwent Breast Conserving Surgery, Masectomy and no Surgery(16 weeks)
- Caspase 3 Activation in Tumor by Immunohistochemistry (IHC) - EAS1(Baseline, Post-baeline at Cycle 1, Day 2 (C1D2) or Cycle 1, Day 9 (C1D9))