FASCINATE-N: Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05582499

Collaborator

(none)

716

Enrollment

Location

Arms

Anticipated Duration (Months)

20.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasm Breast Cancer Breast Tumors Triple-Negative Breast Cancer (TNBC) HER2-positive Breast Cancer HER2-negative Breast Cancer Hormone Receptor Positive Tumor Hormone Receptor Negative Tumor Early-stage Breast Cancer Locally Advanced Breast Cancer	Drug: Dalpiciclib Drug: Pyrotinib Drug: SHR-A1811 Drug: SHR-1316 Drug: Camrelizumab Drug: Trophoblast cell-surface antigen 2 (TROP2) ADC Drug: Pertuzumab Drug: Trastuzumab Drug: Goserelin Drug: Letrozole Drug: Nab paclitaxel Drug: Carboplatin Drug: Epirubicin Drug: Cyclophosphamide Drug: Fluzoparib Drug: HER2 ADC	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

716 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N)

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: L1-1 If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype	Drug: Dalpiciclib an oral cyclin-dependent kinases (CDK) 4/6 inhibitor Other Names: SHR-6390 Drug: Goserelin goserelin Drug: Letrozole letrozole
Active Comparator: L1-2 If patients were HR+HER2- with SNF1 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: L2-1 If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype	Drug: Dalpiciclib an oral cyclin-dependent kinases (CDK) 4/6 inhibitor Other Names: SHR-6390 Drug: SHR-1316 an anti-programmed death ligand 1 (PD-L1) antibody Drug: Goserelin goserelin Drug: Letrozole letrozole
Active Comparator: L2-2 If patients were HR+HER2- with SNF2 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: L3-1 If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype	Drug: Dalpiciclib an oral cyclin-dependent kinases (CDK) 4/6 inhibitor Other Names: SHR-6390 Drug: Goserelin goserelin Drug: Letrozole letrozole Drug: Fluzoparib an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor Other Names: SHR-3162
Active Comparator: L3-2 If patients were HR+HER2- with SNF3 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: L4-1 If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype	Drug: Trophoblast cell-surface antigen 2 (TROP2) ADC anti-TROP2 ADC
Active Comparator: L4-2 If patients were HR+HER2- with SNF4 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: L4-low-1 If patients were HR+HER2-low with SNF4 subtype	Drug: SHR-A1811 an anti-HER2 antibody-drug conjugate (ADC)
Active Comparator: L4-low-2 If patients were HR+HER2-low with SNF4 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: TN1-1 If patients were triple-negative breast cancer with immunomodulatory (IM) subtype	Drug: Camrelizumab an anti-programmed death-1 (PD1) antibody Other Names: SHR-1210 Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Active Comparator: TN1-2 If patients were triple-negative breast cancer with IM subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Experimental: TN2-1 If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide Drug: Fluzoparib an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor Other Names: SHR-3162
Active Comparator: TN2-2 If patients were triple-negative breast cancer with BLIS subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Experimental: TN3-1 If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype	Drug: Pyrotinib an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Active Comparator: TN3-2 If patients were triple-negative breast cancer with AR HER2 subtype	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Experimental: TN4-1 If patients were HR-HER2-low	Drug: SHR-A1811 an anti-HER2 antibody-drug conjugate (ADC)
Active Comparator: TN4-2 If patients were HR-HER2-low	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Experimental: TN5-1 If patients were triple-negative breast cancer with other subtypes	Drug: Trophoblast cell-surface antigen 2 (TROP2) ADC anti-TROP2 ADC
Active Comparator: TN5-2 If patients were triple-negative breast cancer with other subtypes	Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin Drug: Epirubicin Epirubicin Drug: Cyclophosphamide Cyclophosphamide
Experimental: H1-1 If patients were HR+HER2+	Drug: Pyrotinib an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor Drug: HER2 ADC anti-HER2 ADC
Active Comparator: H1-2 If patients were HR+HER2+	Drug: Pertuzumab Pertuzumab Drug: Trastuzumab Trastuzumab Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin
Experimental: H2-1 If patients were HR-HER2+	Drug: HER2 ADC anti-HER2 ADC
Active Comparator: H2-2 If patients were HR-HER2+	Drug: Pertuzumab Pertuzumab Drug: Trastuzumab Trastuzumab Drug: Nab paclitaxel Albumin paclitaxel Drug: Carboplatin Carboplatin

Outcome Measures

Primary Outcome Measures

Pathological complete response rate (pCR) [through study completion, up to 24 weeks]
Pathological complete response rate

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed invasive cancer of the breast and meet the clinical stage T2-4, N1-3, M0 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.