NCT05429684

Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer

Precise Targeted Therapy for Refractory HER2 Positive Advanced Breast Cancer Based on Genome Signature and Drug Sensitivity of PDO Model

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

This is an open, prospective and interventional clinical study. Patients with advanced Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer resistant to trastuzumab will be enrolled in the study. Histological specimens obtained from different metastatic foci of patients, are used to conduct genome-wide sequencing together with Circulating tumor DNA (ctDNA) of blood samples. Meanwhile, investigator will construct PDO model based on biopsy tissue. Patients as well as their paired Patient-derived organoids (PDO) models are divided into six groups according to genomic signatures. Each group of patients will receive the best targeted treatment scheme from the current clinical perspective, while the matched PDO model will accept a variety of potential effective schemes intervention. The future treatment plan of patients will be timely adjusted based on the tumor inhibition rate of PDO models. This study is the first time to explore the best individualized application sequence of targeted therapy for refractory HER2 positive breast cancer by combining genome sequencing with drug sensitivity test of PDO model. The results are expected to improve the prognosis of patients with advanced HER2 positive breast cancer.

Detailed description

In previous studies, investigator found that dynamic genomics detection of metastatic foci can fully reveal the mechanism of trastuzumab resistance. Different anti-HER2 treatment strategies for different mechanisms can improve the efficacy of HER2 positive advanced breast cancer, and the PDO drug sensitivity test model of breast cancer can be prior to patients' response to the exact efficacy of specific regimens.This study aimed to explore the optimal individualized drug combination and order for patients with advanced HER2 positive breast cancer resistant to trastuzumab based on a variety of existing diagnosis and treatment methods. This is an open, prospective and interventional clinical study. Patients with advanced HER2 positive breast cancer resistant to trastuzumab will be enrolled in the study. Histological specimens obtained from different metastatic foci of patients, are used to conduct genome-wide sequencing together with ctDNA of blood samples. Meanwhile, investigator will construct PDO model based on biopsy tissue. Patients as well as their paired PDO models are divided into six groups according to genomic signatures. Each group of patients will receive the best targeted treatment scheme from the current clinical perspective, while the matched PDO model will accept a variety of potential effective schemes intervention. The future treatment plan of patients will be timely adjusted based on the tumor inhibition rate of PDO models. This study is the first time to explore the best individualized application sequence of targeted therapy for refractory HER2 positive breast cancer by combining genome sequencing with drug sensitivity test of PDO model. The results are expected to improve the prognosis of patients with advanced HER2 positive breast cancer.

Conditions

• HER2+ Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab	Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
DRUG	Pertuzumab	Patuzumab (420mg iv.drip, d1,q3w)
DRUG	Nab paclitaxel	nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
DRUG	Pyrotinib	Pyroltinib (400mg po qd)
DRUG	Capecitabine	Capecitabine (1250mg/m2, po, bid, d1-d14, q3w).
DRUG	T-DM1	T-DM1(3.6mg/Kg, iv.drip, d1, q3w)
DRUG	Everolimus	Everolimus (4mg, po, qd)
DRUG	CDK4/6 inhibitor	Palbociclib (125mg, po, qd)
DRUG	AI	Letrozole (2.5mg, qd).
DRUG	Anti-PD-1 monoclonal antibody	Cindilimab (200mg, iv.drip, d1, q3w)

Timeline

• Start date: 2021-01-01
• Primary completion: 2024-02-28
• Completion: 2024-02-28
• First posted: 2022-06-23
• Last updated: 2022-06-23

Locations

2 sites across 1 country: China