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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (5)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

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

Публикации

• 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

Идентификаторы

NCT: NCT05582499 · FASCINATE-N

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗