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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
120

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
First Affiliated Hospital Xi'an Jiaotong University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 12, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 23, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 23, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 20, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings