Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy
Phase 2
Recruiting
- Conditions
- Breast NeoplasmHER2-positive Breast CancerHER2-negative Breast CancerHormone Receptor Positive TumorBreast CancerBreast TumorsHormone Receptor Negative TumorTriple-Negative Breast Cancer (TNBC)Locally Advanced Breast CancerEarly-stage Breast Cancer
- Interventions
- Registration Number
- NCT05582499
- Lead Sponsor
- Fudan University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Female
- Target Recruitment
- 716
Inclusion Criteria
- Histologically confirmed invasive cancer of the breast and meet the clinical stage II（T2N0-1M0/T3N0M0）or III（T2N2M0/T3N1-2M0) criteria;
- 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
Exclusion Criteria
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description L3-2 Nab paclitaxel If patients were HR+HER2- with SNF3 subtype L4-2 Nab paclitaxel If patients were HR+HER2- with SNF4 subtype TN3-1 Nab paclitaxel If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype TN4-2 Nab paclitaxel If patients were HR-HER2-low L4-low-2 Nab paclitaxel If patients were HR+HER2-low with SNF4 subtype TN1-1 Nab paclitaxel If patients were triple-negative breast cancer with immunomodulatory (IM) subtype TN3-2 Nab paclitaxel If patients were triple-negative breast cancer with AR HER2 subtype TN2-2 Nab paclitaxel If patients were triple-negative breast cancer with BLIS subtype H1-2 Nab paclitaxel If patients were HR+HER2+ H2-2 Nab paclitaxel If patients were HR-HER2+ L2-1.2 Nab paclitaxel If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype TN1-1 Camrelizumab If patients were triple-negative breast cancer with immunomodulatory (IM) subtype TN1-1 Carboplatin If patients were triple-negative breast cancer with immunomodulatory (IM) subtype TN1-1 Epirubicin If patients were triple-negative breast cancer with immunomodulatory (IM) subtype TN1-1 Cyclophosphamide If patients were triple-negative breast cancer with immunomodulatory (IM) subtype TN1-2 Nab paclitaxel If patients were triple-negative breast cancer with IM subtype TN1-2 Carboplatin If patients were triple-negative breast cancer with IM subtype TN1-2 Epirubicin If patients were triple-negative breast cancer with IM subtype TN1-2 Cyclophosphamide If patients were triple-negative breast cancer with IM subtype TN2-1 Nab paclitaxel If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype TN2-1 Carboplatin If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype TN2-1 Epirubicin If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype TN2-1 Cyclophosphamide If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype TN2-1 Fluzoparib If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype TN2-2 Carboplatin If patients were triple-negative breast cancer with BLIS subtype TN2-2 Epirubicin If patients were triple-negative breast cancer with BLIS subtype TN2-2 Cyclophosphamide If patients were triple-negative breast cancer with BLIS subtype TN3-1 Pyrotinib If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype TN3-1 Carboplatin If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype TN3-1 Epirubicin If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype TN3-1 Cyclophosphamide If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype TN3-2 Carboplatin If patients were triple-negative breast cancer with AR HER2 subtype TN3-2 Epirubicin If patients were triple-negative breast cancer with AR HER2 subtype TN3-2 Cyclophosphamide If patients were triple-negative breast cancer with AR HER2 subtype TN4-1.1 SHR-A1811 If patients were HR-HER2-low TN4-2 Carboplatin If patients were HR-HER2-low TN4-2 Epirubicin If patients were HR-HER2-low TN4-2 Cyclophosphamide If patients were HR-HER2-low TN5-1.1 SHR-A1921 If patients were triple-negative breast cancer with other subtypes TN5-2 Nab paclitaxel If patients were triple-negative breast cancer with other subtypes TN5-2 Carboplatin If patients were triple-negative breast cancer with other subtypes TN5-2 Epirubicin If patients were triple-negative breast cancer with other subtypes TN5-2 Cyclophosphamide If patients were triple-negative breast cancer with other subtypes H1-1.1 Pyrotinib If patients were HR+HER2+ H1-1.1 SHR-A1811 If patients were HR+HER2+ H1-2 Pertuzumab If patients were HR+HER2+ H1-2 Trastuzumab If patients were HR+HER2+ H1-2 Carboplatin If patients were HR+HER2+ H2-1.1 Pyrotinib If patients were HR-HER2+ H2-2 Pertuzumab If patients were HR-HER2+ H2-2 Trastuzumab If patients were HR-HER2+ H2-2 Carboplatin If patients were HR-HER2+ L2-1.2 SHR-1316 If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype L2-1.2 Carboplatin If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype L3-1.2 Nab paclitaxel If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype L3-1.2 Carboplatin If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype L3-1.2 Fluzoparib If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype L4-1.2 Nab paclitaxel If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype L4-1.2 Carboplatin If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype L4-1.2 Apatinib If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype TN5-1.2 SHR-1316 If patients were triple-negative breast cancer with other subtypes TN5-1.2 SHR-A1921 If patients were triple-negative breast cancer with other subtypes H1-1.2 SHR-A1811 If patients were HR+HER2+ H2-1.2 Pyrotinib If patients were HR-HER2+ H2-1.2 SHR-A1811 If patients were HR-HER2+ TN4-1.2 SHR-A1811 If patients were HR-HER2-low TN4-1.2 Camrelizumab If patients were HR-HER2-low L4-low-2 Carboplatin If patients were HR+HER2-low with SNF4 subtype L1-1 Dalpiciclib If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype L1-1 Goserelin If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype L1-1 Letrozole If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype L1-2 Nab paclitaxel If patients were HR+HER2- with SNF1 subtype L1-2 Carboplatin If patients were HR+HER2- with SNF1 subtype L2-2 Nab paclitaxel If patients were HR+HER2- with SNF2 subtype L2-2 Carboplatin If patients were HR+HER2- with SNF2 subtype L3-2 Carboplatin If patients were HR+HER2- with SNF3 subtype L4-2 Carboplatin If patients were HR+HER2- with SNF4 subtype L4-low-1 SHR-A1811 If patients were HR+HER2-low with SNF4 subtype TN4-1.2 Famitinib If patients were HR-HER2-low
- Primary Outcome Measures
Name Time Method Pathological complete response rate (pCR) through study completion, up to 24 weeks Pathological complete response rate
- Secondary Outcome Measures
Name Time Method invasive disease-free survival (iDFS) Three-year Post-surgery Follow-up To determine three-year invasive disease-free survival (iDFS) among the treatment arms
Overall response rate (ORR) up to 24 weeks Complete response (CR) + partial response (PR)
CTCAE scale (V4.0) through study completion, an average of 1 year 4) To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)
Evaluate gene expression profile during treatment through study completion, up to 24 weeks To measure gene expression profile of baseline and sequential tumor samples during treatment, through RNA-seq platform
Number of peripheral blood mononuclear cells (PBMC) count during treatment through study completion, up to 24 weeks To measure number of peripheral blood mononuclear cells (PBMC) count from baseline and sequential blood samples during treatment, through Flow CytoMetry platform
Trial Locations
- Locations (1)
Fudan University Shanghai Cancer Center Shanghai, China, 200032
🇨🇳Shanghai, Shanghai, China