Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 716
- 试验地点
- 1
- 主要终点
- Pathological complete response rate (pCR)
研究概览
简要总结
The purpose of this study is to establish a prospective, single-center platform research based on clinical subtypes to explore precision neoadjuvant therapy in patients with operable breast cancer who met the indications for neoadjuvant chemotherapy and by the update of basic translational research in the center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs, verified the effectiveness of new targeted drugs in neoadjuvant therapy.
详细描述
FASCINATE-N is a platform that will compare the efficacy of novel drugs alone or in combination with standard chemotherapy with the efficacy of standard therapy alone. The goal is to identify improved treatment regimens for subsets on the basis of clinical subtyping. In this trial, breast cancer patients eligible for inclusion can be randomly divided into the precision treatment group and conventional neoadjuvant chemotherapy group according to molecular typing and subtyping. The research therapy arm can be updated with the update of basic translational research in our center, especially the refinement of typing, the discovery of new targets and the development of novel targeted drugs. As described for previous adaptive trials, regimens that show to be more effective than standard therapy will graduate from the trial with their corresponding biomarker signature(s). Regimens will be dropped if they show a low probability of improved efficacy with any biomarker signature. New drugs will enter as those that have undergone testing complete their evaluation.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed invasive breast cancer of clinical stage T1-4N1-3M0 or cT2-4N0M0;
- •Age between18-70 years;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
- •ER, PR and HER2 status were measured by immunohistochemistry (IHC);
- •LVEF≥55%；
- •Definition of SNF subtypes: SNF subtypes confirmed by digital pathology of H&E slices;
- •Triple negative subtyping: On the basis of triple-negative pathological diagnosis, AR, cluster of differentiation 8 (CD8) and Forkhead Box C1 (FOXC1) were combined to define the subtyping;
- •At least one measurable lesion according to RECIST version 1.1
- •Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine < 1 x ULN, endogenous creatinine clearance > 50 ml/min (Cockcroft-Gault formula);
- •Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug;
- •Ability to understand and willingness to sign a written informed consent
排除标准
- •Previous cytotoxic chemotherapy, endocrine therapy, biological therapy or radiotherapy for any reason;
- •Patients with New York Heart Association (NYHA) grade II or above heart disease (including grade II);
- •Patients with severe systemic infections or other serious diseases;
- •Patients with known allergy or intolerance to the study drug or its excipients;
- •Other malignant tumors in the past 5 years, except cured cervical carcinoma in situ and non-melanoma skin cancer;
- •Pregnant or lactating patients of childbearing age who refused to take appropriate contraceptive measures during the course of the study;
- •Participated in other trial studies within 30 days before the administration of the first dose of the study drug;
- •Patients who were judged by the investigator to be unsuitable for this study.
研究组 & 干预措施
TN9
TNBC
干预措施: paclitaxel (Drug)
H2-2
If patients were HR-HER2+
干预措施: Carboplatin (Drug)
L9
If patients were HR+HER2-low
干预措施: Epirubicin (Drug)
L9
If patients were HR+HER2-low
干预措施: Cyclophosphamide (Drug)
H3
If patients were HER2+
干预措施: JSKN003 (Drug)
L9
If patients were HR+HER2-low
干预措施: Ivonescimab (Drug)
TN6-1
TNBC
干预措施: SHR-A1811 (Drug)
TN6-1
TNBC
干预措施: SHR-1316 (Drug)
TN6-1
TNBC
干预措施: Famitinib (Drug)
TN6-2
TNBC
干预措施: SHR-A1811 (Drug)
TN6-2
TNBC
干预措施: SHR-1316 (Drug)
TN7-1
If patients were HR-HER2-low
干预措施: TQB2102 (Drug)
TN7-1
If patients were HR-HER2-low
干预措施: Benmelstobart (Drug)
TN7-2
If patients were HR-HER2-low
干预措施: TQB2102 (Drug)
TN7-2
If patients were HR-HER2-low
干预措施: Benmelstobart (Drug)
TN8
TNBC
干预措施: TQB2102 (Drug)
H2-2
If patients were HR-HER2+
干预措施: Trastuzumab (Drug)
TN8
TNBC
干预措施: TQB2868 (Drug)
H2-2
If patients were HR-HER2+
干预措施: Nab paclitaxel (Drug)
TN9
TNBC
干预措施: Carboplatin (Drug)
TN9
TNBC
干预措施: Epirubicin (Drug)
L1-1
If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype
干预措施: Dalpiciclib (Drug)
H1-2
If patients were HR+HER2+
干预措施: Nab paclitaxel (Drug)
H1-2
If patients were HR+HER2+
干预措施: Carboplatin (Drug)
L2-2
If patients were HR+HER2- with SNF2 subtype
干预措施: Carboplatin (Drug)
H4-3
If patients were HER2+
干预措施: Carboplatin (Drug)
L3-2
If patients were HR+HER2- with SNF3 subtype
干预措施: Nab paclitaxel (Drug)
H2-1.1
If patients were HR-HER2+
干预措施: Pyrotinib (Drug)
L3-2
If patients were HR+HER2- with SNF3 subtype
干预措施: Carboplatin (Drug)
L4-2
If patients were HR+HER2- with SNF4 subtype
干预措施: Nab paclitaxel (Drug)
L4-2
If patients were HR+HER2- with SNF4 subtype
干预措施: Carboplatin (Drug)
L3-1.1
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Goserelin (Drug)
L4-low-1
If patients were HR+HER2-low with SNF4 subtype
干预措施: SHR-A1811 (Drug)
H4-3
If patients were HER2+
干预措施: Pertuzumab (Drug)
L4-low-2
If patients were HR+HER2-low with SNF4 subtype
干预措施: Nab paclitaxel (Drug)
H4-3
If patients were HER2+
干预措施: Trastuzumab (Drug)
L1-1
If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype
干预措施: Goserelin (Drug)
L4-low-2
If patients were HR+HER2-low with SNF4 subtype
干预措施: Carboplatin (Drug)
L1-1
If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype
干预措施: Letrozole (Drug)
H4-3
If patients were HER2+
干预措施: Nab paclitaxel (Drug)
L1-2
If patients were HR+HER2- with SNF1 subtype
干预措施: Nab paclitaxel (Drug)
L1-2
If patients were HR+HER2- with SNF1 subtype
干预措施: Carboplatin (Drug)
L2-2
If patients were HR+HER2- with SNF2 subtype
干预措施: Nab paclitaxel (Drug)
H1-1.1
If patients were HR+HER2+
干预措施: Pyrotinib (Drug)
H1-1.1
If patients were HR+HER2+
干预措施: SHR-A1811 (Drug)
H1-2
If patients were HR+HER2+
干预措施: Pertuzumab (Drug)
L5-1
If patients were HR+HER2-
干预措施: LEM (Drug)
L5-2
If patients were HR+HER2-
干预措施: LEM (Drug)
H1-2
If patients were HR+HER2+
干预措施: Trastuzumab (Drug)
TN1-1
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
干预措施: Camrelizumab (Drug)
TN1-1
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
干预措施: Nab paclitaxel (Drug)
TN1-1
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
干预措施: Carboplatin (Drug)
TN1-1
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
干预措施: Epirubicin (Drug)
TN1-1
If patients were triple-negative breast cancer with immunomodulatory (IM) subtype
干预措施: Cyclophosphamide (Drug)
TN1-2
If patients were triple-negative breast cancer with IM subtype
干预措施: Nab paclitaxel (Drug)
TN1-2
If patients were triple-negative breast cancer with IM subtype
干预措施: Carboplatin (Drug)
TN1-2
If patients were triple-negative breast cancer with IM subtype
干预措施: Epirubicin (Drug)
TN1-2
If patients were triple-negative breast cancer with IM subtype
干预措施: Cyclophosphamide (Drug)
TN2-1
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
干预措施: Nab paclitaxel (Drug)
TN2-1
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
干预措施: Carboplatin (Drug)
TN2-1
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
干预措施: Epirubicin (Drug)
TN2-1
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
干预措施: Cyclophosphamide (Drug)
TN2-1
If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype
干预措施: Fluzoparib (Drug)
TN2-2
If patients were triple-negative breast cancer with BLIS subtype
干预措施: Nab paclitaxel (Drug)
TN2-2
If patients were triple-negative breast cancer with BLIS subtype
干预措施: Carboplatin (Drug)
TN2-2
If patients were triple-negative breast cancer with BLIS subtype
干预措施: Epirubicin (Drug)
TN2-2
If patients were triple-negative breast cancer with BLIS subtype
干预措施: Cyclophosphamide (Drug)
TN3-1
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
干预措施: Pyrotinib (Drug)
TN3-1
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
干预措施: Nab paclitaxel (Drug)
TN3-1
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
干预措施: Carboplatin (Drug)
TN3-1
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
干预措施: Epirubicin (Drug)
TN3-1
If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype
干预措施: Cyclophosphamide (Drug)
TN3-2
If patients were triple-negative breast cancer with AR HER2 subtype
干预措施: Nab paclitaxel (Drug)
TN3-2
If patients were triple-negative breast cancer with AR HER2 subtype
干预措施: Carboplatin (Drug)
TN3-2
If patients were triple-negative breast cancer with AR HER2 subtype
干预措施: Epirubicin (Drug)
TN3-2
If patients were triple-negative breast cancer with AR HER2 subtype
干预措施: Cyclophosphamide (Drug)
TN4-1.1
If patients were HR-HER2-low
干预措施: SHR-A1811 (Drug)
TN4-2
If patients were HR-HER2-low
干预措施: Nab paclitaxel (Drug)
TN4-2
If patients were HR-HER2-low
干预措施: Carboplatin (Drug)
TN4-2
If patients were HR-HER2-low
干预措施: Epirubicin (Drug)
TN4-2
If patients were HR-HER2-low
干预措施: Cyclophosphamide (Drug)
TN5-1.1
If patients were triple-negative breast cancer with other subtypes
干预措施: SHR-A1921 (Drug)
TN5-2
If patients were triple-negative breast cancer with other subtypes
干预措施: Nab paclitaxel (Drug)
TN5-2
If patients were triple-negative breast cancer with other subtypes
干预措施: Carboplatin (Drug)
TN5-2
If patients were triple-negative breast cancer with other subtypes
干预措施: Epirubicin (Drug)
TN5-2
If patients were triple-negative breast cancer with other subtypes
干预措施: Cyclophosphamide (Drug)
H2-2
If patients were HR-HER2+
干预措施: Pertuzumab (Drug)
L2-1.2
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: SHR-1316 (Drug)
L2-1.2
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Nab paclitaxel (Drug)
L2-1.2
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Carboplatin (Drug)
L3-1.2
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Nab paclitaxel (Drug)
L3-1.2
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Carboplatin (Drug)
L3-1.2
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Fluzoparib (Drug)
L4-1.2
If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype
干预措施: Nab paclitaxel (Drug)
L4-1.2
If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype
干预措施: Carboplatin (Drug)
L4-1.2
If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype
干预措施: Apatinib (Drug)
TN5-1.2
If patients were triple-negative breast cancer with other subtypes
干预措施: SHR-1316 (Drug)
TN5-1.2
If patients were triple-negative breast cancer with other subtypes
干预措施: SHR-A1921 (Drug)
H1-1.2
If patients were HR+HER2+
干预措施: SHR-A1811 (Drug)
H2-1.2
If patients were HR-HER2+
干预措施: Pyrotinib (Drug)
H2-1.2
If patients were HR-HER2+
干预措施: SHR-A1811 (Drug)
TN4-1.2
If patients were HR-HER2-low
干预措施: SHR-A1811 (Drug)
TN4-1.2
If patients were HR-HER2-low
干预措施: Camrelizumab (Drug)
TN4-1.2
If patients were HR-HER2-low
干预措施: Famitinib (Drug)
L2-1.1
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Dalpiciclib (Drug)
L2-1.1
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Goserelin (Drug)
L2-1.1
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Letrozole (Drug)
L2-1.3
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: SHR-1316 (Drug)
L2-1.3
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Nab paclitaxel (Drug)
L2-1.3
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Carboplatin (Drug)
L2-1.3
If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype
干预措施: Famitinib (Drug)
L3-1.1
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Dalpiciclib (Drug)
L3-1.1
If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype
干预措施: Letrozole (Drug)
L4-1.1
If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype
干预措施: SHR-A1921 (Drug)
L5-1
If patients were HR+HER2-
干预措施: Cyclophosphamide (Drug)
L5-1
If patients were HR+HER2-
干预措施: HB1801 (Drug)
L5-2
If patients were HR+HER2-
干预措施: Cyclophosphamide (Drug)
L5-2
If patients were HR+HER2-
干预措施: HB1801 (Drug)
L6
If patients were HR+HER2-low
干预措施: SHR-A1811 (Drug)
L6
If patients were HR+HER2-low
干预措施: SHR-1316 (Drug)
L6
If patients were HR+HER2-low
干预措施: Famitinib (Drug)
L7
If patients were HR+HER2-low
干预措施: Famitinib (Drug)
L7
If patients were HR+HER2-low
干预措施: TQB2102 (Drug)
L7
If patients were HR+HER2-low
干预措施: Benmelstobart (Drug)
L8
If patients were HR+HER2-
干预措施: TQB2102 (Drug)
L8
If patients were HR+HER2-
干预措施: Anlotinib (Drug)
L8
If patients were HR+HER2-
干预措施: TQB2868 (Drug)
L9
If patients were HR+HER2-low
干预措施: Nab paclitaxel (Drug)
L9
If patients were HR+HER2-low
干预措施: Carboplatin (Drug)
TN7-2
If patients were HR-HER2-low
干预措施: Anlotinib (Drug)
TN9
TNBC
干预措施: Cyclophosphamide (Drug)
H4-1
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H4-1
If patients were HER2+
干预措施: Pertuzumab (Drug)
H4-1
If patients were HER2+
干预措施: Trastuzumab (Drug)
H4-1
If patients were HER2+
干预措施: Nab paclitaxel (Drug)
H4-1
If patients were HER2+
干预措施: Carboplatin (Drug)
H4-2
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H4-4
If patients were HER2+
干预措施: Pyrotinib (Drug)
H4-4
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H5
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H5
If patients were HER2+
干预措施: SHR-4602 (Drug)
H6-1
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H6-1
If patients were HER2+
干预措施: HRS-4508 (Drug)
H6-2
If patients were HER2+
干预措施: SHR-A1811 (Drug)
H6-2
If patients were HER2+
干预措施: Pertuzumab (Drug)
H6-2
If patients were HER2+
干预措施: HRS-4508 (Drug)
L10
If patients were HR+HER2-
干预措施: Nab paclitaxel (Drug)
L10
If patients were HR+HER2-
干预措施: Epirubicin (Drug)
L10
If patients were HR+HER2-
干预措施: Cyclophosphamide (Drug)
L10
If patients were HR+HER2-
干预措施: JS207 (Drug)
结局指标
主要结局
Pathological complete response rate (pCR)
时间窗: through study completion, up to 24 weeks
Pathological complete response rate
次要结局
- CTCAE scale (V4.0)(through study completion, an average of 1 year)
- invasive disease-free survival (iDFS)(Three-year Post-surgery Follow-up)
- Overall response rate (ORR)(up to 24 weeks)
- Evaluate gene expression profile during treatment(through study completion, up to 24 weeks)
- Number of peripheral blood mononuclear cells (PBMC) count during treatment(through study completion, up to 24 weeks)