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

Official title

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

Overview

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.

Interventions

• Drug Dalpiciclib
  an oral cyclin-dependent kinases (CDK) 4/6 inhibitor
• Drug Pyrotinib
  an irreversible dual pan-erbb receptor tyrosine kinase receptor tyrosine kinase (ERBB) inhibitor
• Drug SHR-A1811
  an anti-HER2 antibody-drug conjugate (ADC)
• Drug SHR-1316
  an anti-programmed death ligand 1 (PD-L1) antibody
• Drug Camrelizumab
  an anti-programmed death-1 (PD1) antibody
• Drug SHR-A1921
  Trophoblast cell-surface antigen 2 (TROP2) ADC
• Drug Pertuzumab
  Pertuzumab
• Drug Trastuzumab
  Trastuzumab
• Drug Goserelin
  goserelin
• Drug Letrozole
  letrozole

Primary outcome measures

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

Secondary outcome measures (5)

• invasive disease-free survival (iDFS) [Time frame: Three-year Post-surgery Follow-up]
• Overall response rate (ORR) [Time frame: up to 24 weeks]
• CTCAE scale (V4.0) [Time frame: through study completion, an average of 1 year]
• Evaluate gene expression profile during treatment [Time frame: through study completion, up to 24 weeks]
• Number of peripheral blood mononuclear cells (PBMC) count during treatment [Time frame: through study completion, up to 24 weeks]

Eligibility criteria

Inclusion criteria

• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Fudan University Shanghai Cancer Center Shanghai, China, 200032 — Shanghai

Publications

• Zuo WJ, Chen L, Shen Y, Wang ZH, Liu GY, Yu KD, Di GH, Wu J, Li JJ, Shao ZM. Rational and trial design of FASCINATE-N: a prospective, randomized, precision-based umbrella trial. Ther Adv Med Oncol. 2024 Feb 14;16:17588359231225032. doi: 10.1177/17588359231225032. eCollection 2024. PMID 38362377

Identifiers

NCT: NCT05582499 · FASCINATE-N

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗