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Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT05429684
Recruitment Status : Recruiting
First Posted : June 23, 2022
Last Update Posted : June 23, 2022
Sponsor:
Information provided by (Responsible Party):
First Affiliated Hospital Xi'an Jiaotong University

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.

Condition or disease Intervention/treatment Phase
HER2+ Breast Cancer Drug: Trastuzumab Drug: Pertuzumab Drug: Nab paclitaxel Drug: Pyrotinib Drug: Capecitabine Drug: T-DM1 Drug: Everolimus Drug: CDK4/6 inhibitor Drug: AI Drug: Anti-PD-1 monoclonal antibody Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Precise Targeted Therapy for Refractory HER2 Positive Advanced Breast Cancer Based on Genome Signature and Drug Sensitivity of PDO Model
Actual Study Start Date : January 1, 2021
Estimated Primary Completion Date : February 28, 2024
Estimated Study Completion Date : February 28, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: herceptin;Inetetamab

Drug: Pertuzumab
Patuzumab (420mg iv.drip, d1,q3w)
Other Name: Perjeta

Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Name: Abraxane

Experimental: B. HER2 amplified
Signatured by wild type HER2 amplified.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Name: herceptin;Inetetamab

Drug: Pertuzumab
Patuzumab (420mg iv.drip, d1,q3w)
Other Name: Perjeta

Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Name: Abraxane

Experimental: C. HER2 mutation
Signatured by HER2 mutation.
Drug: Pyrotinib
Pyroltinib (400mg po qd)
Other Name: 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 Name: herceptin;Inetetamab

Drug: Nab paclitaxel
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
Other Name: Abraxane

Drug: T-DM1
T-DM1(3.6mg/Kg, iv.drip, d1, q3w)
Other Name: Trastuzumab Emtansine

Drug: Everolimus
Everolimus (4mg, po, qd)
Other Name: 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 Name: herceptin;Inetetamab

Drug: CDK4/6 inhibitor
Palbociclib (125mg, po, qd)
Other Name: Palbociclib;

Drug: AI
Letrozole (2.5mg, qd).
Other Name: Letrozole

Experimental: F. Immune activation
Signatured by high TMB or PD-L1 positively expressed.
Drug: Trastuzumab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
Other Name: herceptin;Inetetamab

Drug: Anti-PD-1 monoclonal antibody
Cindilimab (200mg, iv.drip, d1, q3w)
Other Name: Sintilimab




Primary Outcome Measures :
  1. ORR [ Time Frame: Up to six weeks, first evaluation ]
    objective response rate (ORR) according to RECIST (version 1.1) of each group

  2. PDO model inhibition rate [ Time Frame: during the procedure ]
    Tumor regression rate based on the calculation of the long diameter in each group


Secondary Outcome Measures :
  1. PFS1 [ Time Frame: during the procedure ]
    Progress free survival (PFS) according to RECIST (version 1.1) of each group



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05429684


Contacts
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Contact: Jin Yang, Doctor +862985323473 792171443@qq.com

Locations
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China, Shaanxi
The First Affiliated Hospital of Xi'an Jiaotong University Recruiting
Xi'an, Shaanxi, China, 710000
Contact: Jin Yang, PhD    0086-18991232383    1473106133@qq.com   
Jin Yang Recruiting
Xi'an, Shaanxi, China, 710061
Contact: Jin Yang    +862985324600    1473106133@qq.com   
Sponsors and Collaborators
First Affiliated Hospital Xi'an Jiaotong University
Investigators
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Principal Investigator: Jin Yang, Doctor First Affiliated Hospital Xi'an Jiaotong University
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Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
ClinicalTrials.gov Identifier: NCT05429684    
Other Study ID Numbers: XJTU1AF-CRF-2020-006
First Posted: June 23, 2022    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ado-Trastuzumab Emtansine
Capecitabine
Trastuzumab
Everolimus
Letrozole
Palbociclib
Pertuzumab
Antibodies
Antibodies, Monoclonal
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological
Immunosuppressive Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists