Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer

HER2+ Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05429684
• Other study ID #: XJTU1AF-CRF-2020-006
• Status: Recruiting
• Phase: Phase 3
• Start date: January 1, 2021
• Est. completion date: February 28, 2024

Study information

• Verified date: May 2022
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: Jin Yang, Doctor
• Phone: +862985323473
• Email: 792171443[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: February 28, 2024
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2+ Breast Cancer

Intervention

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

Locations

Country	Name	City	State
China	Jin Yang	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	objective response rate (ORR) according to RECIST (version 1.1) of each group	Up to six weeks, first evaluation
Primary	PDO model inhibition rate	Tumor regression rate based on the calculation of the long diameter in each group	during the procedure
Secondary	PFS1	Progress free survival (PFS) according to RECIST (version 1.1) of each group	during the procedure