HER2+ Breast Cancer
Conditions
Brief 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.
Interventions
DRUGAnti-PD-1 monoclonal antibody
Cindilimab (200mg, iv.drip, d1, q3w)
DRUGTrastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
DRUGPertuzumab
Patuzumab (420mg iv.drip, d1,q3w)
DRUGNab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
DRUGPyrotinib
Pyroltinib (400mg po qd)
DRUGCapecitabine
Capecitabine (1250mg/m2, po, bid, d1-d14, q3w).
DRUGT-DM1
T-DM1(3.6mg/Kg, iv.drip, d1, q3w)
DRUGEverolimus
Everolimus (4mg, po, qd)
DRUGCDK4/6 inhibitor
Palbociclib (125mg, po, qd)
DRUGAI
Letrozole (2.5mg, qd).
Sponsors
First Affiliated Hospital Xi'an Jiaotong University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. 18-70 years old; 2. Women; 3. ECOG score 0-2; 4. Locally advanced or metastatic breast cancer confirmed by histopathology; 5. Positive HER2 expression in cancer tissues (IHC 3 +, or IHC 2 + but FISH amplification); 6. Resistant to trastuzumab (including disease progression during or after withdrawal of trastuzumab); 7. There were enough specimens for immunohistochemistry, gene detection and establishment of PDO model; 8. Hematology and liver and kidney function were normal within 2 weeks before treatment; 9. Imaging examination showed measurable lesions (according to RECIST v1.1); 10. Women of childbearing age agree to contraception or take contraceptive measures; 11. Be able to understand the research program and participate voluntarily.
Exclusion criteria
1. Symptomatic, untreated or progressive central nervous system metastases; 2. Severe heart disease (poor cardiac function); 3. Within 5 years, there was a history of other malignant tumors other than breast cancer; 4. In this study, chemotherapy, radiotherapy, immunotherapy or surgery were performed within 3 weeks before the first treatment; 5. Patients who are pregnant or lactating, or plan to become pregnant during enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Up to six weeks, first evaluation | objective response rate (ORR) according to RECIST (version 1.1) of each group |
| PDO model inhibition rate | during the procedure | Tumor regression rate based on the calculation of the long diameter in each group |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS1 | during the procedure | Progress free survival (PFS) according to RECIST (version 1.1) of each group |
Countries
China
Contacts
Primary ContactJin Yang, Doctor
Outcome results
None listed