Clinical trial NCT05582499: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: 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
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-10-17
Enrollment: 716
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathological complete response rate (pCR)
timeFrame: through study completion, up to 24 weeks
Secondary outcomes:
measure: invasive disease-free survival (iDFS)
timeFrame: Three-year Post-surgery Follow-up
measure: Overall response rate (ORR)
timeFrame: up to 24 weeks
measure: CTCAE scale (V4.0)
timeFrame: through study completion, an average of 1 year
measure: Evaluate gene expression profile during treatment
timeFrame: through study completion, up to 24 weeks
measure: Number of peripheral blood mononuclear cells (PBMC) count during treatment
timeFrame: through study completion, up to 24 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center Shanghai, China, 200032
state: Shanghai
Study officials:
affiliation: Fudan University
name: Zhimin Shao, Professor
role: PRINCIPAL_INVESTIGATOR
References: