PRESENT: Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer With Low to Intermediate HER2 Expressions With NeuVax™Treatment
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 758
- 试验地点
- 386
- 主要终点
- Comparison of DFS in vaccine treated patients and control patients
研究概览
简要总结
Purpose of this trial:
- To assess the efficacy and safety of NeuVax™ administered with adjuvant Leukine® (sargramostim, GM-CSF).
- To evaluate and compare the disease free survival (DFS) in the vaccinated and control subjects.
详细描述
This is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study.
The subjects eligible for this trial have an early stage node-positive breast cancer. Their tumors express low or intermediate levels of the HER2 protein. NeuVax™ will be administered after completion of front-line, standard of care therapy (surgery, radiation therapy, and chemotherapy) and can be given concomitantly with physician prescribed endocrine treatment.
NeuVax™ is the immmunodominant nonapeptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. The nelipepimut sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTL) following binding to HLA-A2/A3 molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy through cell lysis HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading. Based on a successful Phase 2 trial, which achieved its primary endpoint of DFS, the Food and Drug Administration (FDA) granted NeuVax a Special Protocol Assessment (SPA) for its Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study.
The active portion of the study will last three years (36 months). The follow-up will last from 5 to 10 years.
Endpoints:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Pathological diagnosis of invasive adenocarcinoma of the breast
- •Breast cancer completely excised, or patient receiving neoadjuvant therapy prior to surgery
- •One of these 2 surgical treatments and axillary staging with sentinel lymph node dissection or axillary dissection level I/II:
- •Total mastectomy-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II
- •BCS (lumpectomy)-patients with a positive sentinel lymph node must have undergone a completion axillary dissection level I/II unless they had clinically node negative T1-T2 tumors and fewer than 3 involved lymph nodes
- •Node-positive disease
- •Primary tumor stage T1-3 at initial diagnosis
- •HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
- •HLA-A2 or HLA-A3 haplotype
- •Completed NCCN approved neo-adjuvant/adjuvant chemotherapy or both
- •Completed radiation therapy
- •No evidence of disease
- •Able and willing (or have legal representative) to understand the study and provide consent
排除标准
- •Bilateral breast malignancy or suspicious mass in opposite breast
- •Inflammatory breast malignancy
- •History of prior breast cancer, ductal carcinoma in situ
- •Prior trastuzumab therapy
- •New York Heart Association Stage 3 or 4 cardiac disease
- •Sensory/motor neuropathy ≥ Grade 2
- •Autoimmune diseases or immune deficiency disease
- •Subjects on chronic steroid therapy, other immunosuppressive therapy
结局指标
主要结局
Comparison of DFS in vaccine treated patients and control patients
时间窗: 36 months
The primary objective is to compare the DFS in subjects with operable early-stage, node-positive breast cancer who receive standard of care multimodality therapy plus NeuVax™ as the treatment group or standard of care multimodality therapy plus the vaccine adjuvant, Leukine® as the control group.
次要结局
- Assessment of DFS and OS at 3, 5 and 10 years in vaccine and control groups, respectively; assessment of safety(3 through 10 years)