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

Breast Cancer Clinical Trial

— FASCINATE-N  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05582499
• Other study ID #: FASCINATE-N
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 1, 2022
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: Fudan University
• Contact: Zhimin Shao, Professor
• Phone: +86(021)64175590
• Email: zhimingshao[@]yahoo.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 716
• Est. completion date: September 2025
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dalpiciclib
an oral cyclin-dependent kinases (CDK) 4/6 inhibitor
• Pyrotinib
an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
• SHR-A1811
an anti-HER2 antibody-drug conjugate (ADC)
• SHR-1316
an anti-programmed death ligand 1 (PD-L1) antibody
• Camrelizumab
an anti-programmed death-1 (PD1) antibody
• Trophoblast cell-surface antigen 2 (TROP2) ADC
anti-TROP2 ADC
• Pertuzumab
Pertuzumab
• Trastuzumab
Trastuzumab
• Goserelin
goserelin
• Letrozole
letrozole
• Nab paclitaxel
Albumin paclitaxel
• Carboplatin
Carboplatin
• Epirubicin
Epirubicin
• Cyclophosphamide
Cyclophosphamide
• Fluzoparib
an original poly adenosine diphosphate-ribose polymerase (PARP) inhibitor
• HER2 ADC
anti-HER2 ADC

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center Shanghai, China, 200032	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response rate (pCR)	Pathological complete response rate	through study completion, up to 24 weeks
Secondary	invasive disease-free survival (iDFS)	To determine three-year invasive disease-free survival (iDFS) among the treatment arms	Three-year Post-surgery Follow-up
Secondary	Overall response rate (ORR)	Complete response (CR) + partial response (PR)	up to 24 weeks
Secondary	CTCAE scale (V4.0)	4) To evaluate the rate of adverse effects of patient by the standard CTCAE scale (V4.0)	through study completion, an average of 1 year
Secondary	Evaluate gene expression profile during treatment	To measure gene expression profile of baseline and sequential tumor samples during treatment, through RNA-seq platform	through study completion, up to 24 weeks
Secondary	Number of peripheral blood mononuclear cells (PBMC) count during treatment	To measure number of peripheral blood mononuclear cells (PBMC) count from baseline and sequential blood samples during treatment, through Flow CytoMetry platform	through study completion, up to 24 weeks