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

Fudan University

Status and phase: Enrolling; Phase 2

Conditions: Breast Tumors; Breast Cancer; Breast Neoplasm; Locally Advanced Breast Cancer; Hormone Receptor Negative Tumor; Early-stage Breast Cancer; Hormone Receptor Positive Tumor; HER2-positive Breast Cancer; HER2-negative Breast Cancer; Triple-Negative Breast Cancer (TNBC)

Treatments: Drug: Fluzoparib; Drug: Cyclophosphamide; Drug: Camrelizumab; Drug: Epirubicin; Drug: Trastuzumab; Drug: Nab paclitaxel; Drug: Goserelin; Drug: SHR-A1811; Drug: Famitinib; Drug: SHR-A1921; Drug: Apatinib; Drug: SHR-1316; Drug: Pyrotinib; Drug: Carboplatin; Drug: Pertuzumab; Drug: Letrozole; Drug: Dalpiciclib

Study type: Interventional

Funder types: Other

Identifiers

NCT05582499

FASCINATE-N

Details and patient eligibility

About

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.

Full 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.

Enrollment: 716 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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716 participants in 28 patient groups

L1-1

Experimental group

Description:

If patients were hormone receptor-positive (HR+) and HER2-negative (HER2-) defined as similarity network fusion 1(SNF1) subtype

Treatment:

Drug: Dalpiciclib

Drug: Letrozole

Drug: Goserelin

L1-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF1 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

L2-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF2 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

L3-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF3 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

L4-2

Active Comparator group

Description:

If patients were HR+HER2- with SNF4 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

L4-low-1

Experimental group

Description:

If patients were HR+HER2-low with SNF4 subtype

Treatment:

Drug: SHR-A1811

L4-low-2

Active Comparator group

Description:

If patients were HR+HER2-low with SNF4 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

TN1-1

Experimental group

Description:

If patients were triple-negative breast cancer with immunomodulatory (IM) subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Camrelizumab

Drug: Cyclophosphamide

TN1-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with IM subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

TN2-1

Experimental group

Description:

If patients were triple-negative breast cancer with basal-like immune suppressed (BLIS) subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Fluzoparib

Drug: Cyclophosphamide

TN2-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with BLIS subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

TN3-1

Experimental group

Description:

If patients were triple-negative breast cancer with androgen receptor positive HER2 activated (AR HER2) subtype

Treatment:

Drug: Carboplatin

Drug: Pyrotinib

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

TN3-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with AR HER2 subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

TN4-1.1

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: SHR-A1811

TN4-2

Active Comparator group

Description:

If patients were HR-HER2-low

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

TN5-1.1

Experimental group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: SHR-A1921

TN5-2

Active Comparator group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Epirubicin

Drug: Cyclophosphamide

H1-1.1

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: Pyrotinib

Drug: SHR-A1811

H1-2

Active Comparator group

Description:

If patients were HR+HER2+

Treatment:

Drug: Carboplatin

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Trastuzumab

H2-1.1

Experimental group

Description:

If patients were HR-HER2+

Treatment:

Drug: Pyrotinib

H2-2

Active Comparator group

Description:

If patients were HR-HER2+

Treatment:

Drug: Carboplatin

Drug: Pertuzumab

Drug: Nab paclitaxel

Drug: Trastuzumab

L2-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 2 (SNF2) subtype

Treatment:

Drug: Carboplatin

Drug: SHR-1316

Drug: Nab paclitaxel

L3-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 3 (SNF3) subtype

Treatment:

Drug: Carboplatin

Drug: Nab paclitaxel

Drug: Fluzoparib

L4-1.2

Experimental group

Description:

If patients were HR+HER2- with similarity network fusion 4 (SNF4) subtype

Treatment:

Drug: Carboplatin

Drug: Apatinib

Drug: Nab paclitaxel

TN5-1.2

Experimental group

Description:

If patients were triple-negative breast cancer with other subtypes

Treatment:

Drug: SHR-1316

Drug: SHR-A1921

H1-1.2

Experimental group

Description:

If patients were HR+HER2+

Treatment:

Drug: SHR-A1811

H2-1.2

Experimental group

Description:

If patients were HR-HER2+

Treatment:

Drug: Pyrotinib

Drug: SHR-A1811

TN4-1.2

Experimental group

Description:

If patients were HR-HER2-low

Treatment:

Drug: Famitinib

Drug: SHR-A1811

Drug: Camrelizumab