NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
研究概览
简要总结
This randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting).
详细描述
NeoPHOEBE evaluated the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer >1.5 cm (by US or MRI) with centrally confirmed HER2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer.
Prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus BKM120 or placebo only. The study was conducted separately in two cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each cohort patients were randomized into one of the following treatment arms:
Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.
Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.
After completion of study treatment, patients were to have undergone definitive surgery.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Patient had provided a signed study ICF prior to any screening procedure
- •Patient was a female ≥ 18 years of age
- •Patient has an ECOG performance status of 0-1
- •Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or >1.5 cm confirmed by ultrasound or by MRI
- •Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status
- •Patient has adequate bone marrow, renal and liver function
- •Patient is able to swallow and retain oral medication
排除标准
- •Patient has received prior systemic treatment for currently diagnosed disease
- •Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor
- •Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer
- •LVEF below 50% as determined by MUGA scan or ECHO
- •Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol
- •Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
- •Patient is currently receiving warfarin or other coumarin derived anti-coagulants
- •Patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed)
- •Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of CYP3A
- •Patient has certain scores on an anxiety and depression mood questionnaires
- •Pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol
研究组 & 干预措施
BKM120 + Trastuzumab + paclitaxel
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
干预措施: BKM120 (Drug)
BKM120 + Trastuzumab + paclitaxel
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
干预措施: Trastuzumab (Drug)
BKM120 + Trastuzumab + paclitaxel
BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
干预措施: Paclitaxel (Drug)
BKM120 PBO + Trastuzumab + paclitaxel
BKM120 placebo in combination with trastuzumab and paclitaxel
干预措施: Trastuzumab (Drug)
BKM120 PBO + Trastuzumab + paclitaxel
BKM120 placebo in combination with trastuzumab and paclitaxel
干预措施: Paclitaxel (Drug)
BKM120 PBO + Trastuzumab + paclitaxel
BKM120 placebo in combination with trastuzumab and paclitaxel
干预措施: BKM120 Placebo (Drug)
结局指标
主要结局
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
时间窗: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast \[ypT0\]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
时间窗: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast \[ypT0\]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
时间窗: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast \[ypT0\]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
次要结局
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants(After week 6)
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants(After week 6)
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants(After week 6)
- Rate of Breast Conserving Surgery (Most Radical Surgery)(18 weeks)
- Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition(After Week 6)
- Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition(After Week 6)
- Overall Objective Response Rate (ORR) Prior to Surgery for All Participants(prior to surgery)
- Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)(After Week 6)
- Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)(After Week 6)
- Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)(After Week 6)
- Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)(After Week 6)
- Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)(18 weeks)
- Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)(18 weeks)