Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer

June 20, 2022 updated by: First Affiliated Hospital Xi'an Jiaotong University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shaanxi
      • Xi'an, Shaanxi, China, 710000
        • Recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Contact:
      • Xi'an, Shaanxi, China, 710061
        • Recruiting
        • Jin Yang
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A. HER2 low expression
Phenotype was signatured by HER2 low expression.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • herceptin；Inetetamab
Drug: Pertuzumab
Patuzumab (420mg iv.drip, d1,q3w)
Other Names:
  • Perjeta
Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Names:
  • Abraxane
Experimental: B. HER2 amplified
Signatured by wild type HER2 amplified.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • herceptin；Inetetamab
Drug: Pertuzumab
Patuzumab (420mg iv.drip, d1,q3w)
Other Names:
  • Perjeta
Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Names:
  • Abraxane
Experimental: C. HER2 mutation
Signatured by HER2 mutation.
Drug: Pyrotinib
Pyroltinib (400mg po qd)
Other Names:
  • SHR-1258
Drug: Capecitabine
Capecitabine (1250mg/m2, po, bid, d1-d14, q3w).
Experimental: D. HER2 downstream mutation
Signatured by HER2 downstream mutation of PI3KCA, TP53 or PTEN.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • herceptin；Inetetamab
Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Names:
  • Abraxane
Drug: T-DM1
T-DM1(3.6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • Trastuzumab Emtansine
Drug: Everolimus
Everolimus (4mg, po, qd)
Other Names:
  • RAD001
Experimental: E. Hormone receptor pathway activation
Signatured by both ER and PR strongly expressed,or CCND1 amplified.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • herceptin；Inetetamab
Drug: CDK4/6 inhibitor
Palbociclib (125mg, po, qd)
Other Names:
  • Palbociclib；
Drug: AI
Letrozole (2.5mg, qd).
Other Names:
  • Letrozole
Experimental: F. Immune activation
Signatured by high TMB or PD-L1 positively expressed.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Names:
  • herceptin；Inetetamab
Drug: Anti-PD-1 monoclonal antibody
Cindilimab (200mg, iv.drip, d1, q3w)
Other Names:
  • Sintilimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ORR
Time Frame: Up to six weeks, first evaluation
objective response rate (ORR) according to RECIST (version 1.1) of each group
Up to six weeks, first evaluation
PDO model inhibition rate
Time Frame: during the procedure
Tumor regression rate based on the calculation of the long diameter in each group
during the procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS1
Time Frame: during the procedure
Progress free survival (PFS) according to RECIST (version 1.1) of each group
during the procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Investigators

  • Principal Investigator: Jin Yang, Doctor, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2021

Primary Completion (Anticipated)

February 28, 2024

Study Completion (Anticipated)

February 28, 2024

Study Registration Dates

First Submitted

December 12, 2021

First Submitted That Met QC Criteria

June 20, 2022

First Posted (Actual)

June 23, 2022

Study Record Updates

Last Update Posted (Actual)

June 23, 2022

Last Update Submitted That Met QC Criteria

June 20, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XJTU1AF-CRF-2020-006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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