Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer

NCT05429684 | Unknown Phase 3

• 1 other identifier: XJTU1AF-CRF-2020-006
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

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.

Conditions

HER2+ Breast Cancer

Outcome Measures

Primary Outcomes (2)

• ORR

  objective response rate (ORR) according to RECIST (version 1.1) of each group

  Up to six weeks, first evaluation

• PDO model inhibition rate

  Tumor regression rate based on the calculation of the long diameter in each group

  during the procedure

Secondary Outcomes (1)

• PFS1

  during the procedure

Study Arms (6)

A. HER2 low expression

EXPERIMENTAL

Phenotype was signatured by HER2 low expression.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab paclitaxel

B. HER2 amplified

EXPERIMENTAL

Signatured by wild type HER2 amplified.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab paclitaxel

C. HER2 mutation

EXPERIMENTAL

Signatured by HER2 mutation.

Drug: Pyrotinib; Drug: Capecitabine

D. HER2 downstream mutation

EXPERIMENTAL

Signatured by HER2 downstream mutation of PI3KCA, TP53 or PTEN.

Drug: Trastuzumab; Drug: Nab paclitaxel; Drug: T-DM1; Drug: Everolimus

E. Hormone receptor pathway activation

EXPERIMENTAL

Signatured by both ER and PR strongly expressed,or CCND1 amplified.

Drug: Trastuzumab; Drug: CDK4/6 inhibitor; Drug: AI

F. Immune activation

EXPERIMENTAL

Signatured by high TMB or PD-L1 positively expressed.

Drug: Trastuzumab; Drug: Anti-PD-1 monoclonal antibody

Interventions

Trastuzumab DRUG

Trastuzumab (6mg/Kg, iv.drip, d1, q3w)

Also known as: herceptin；Inetetamab

A. HER2 low expression; B. HER2 amplified; D. HER2 downstream mutation; E. Hormone receptor pathway activation; F. Immune activation

Pertuzumab DRUG

Patuzumab (420mg iv.drip, d1,q3w)

Also known as: Perjeta

A. HER2 low expression; B. HER2 amplified

Nab paclitaxel DRUG

nab-paclitaxel (200mg iv.drip, d1,d8, q3w)

Also known as: Abraxane

A. HER2 low expression; B. HER2 amplified; D. HER2 downstream mutation

Pyrotinib DRUG

Pyroltinib (400mg po qd)

Also known as: SHR-1258

C. HER2 mutation

Capecitabine DRUG

Capecitabine (1250mg/m2, po, bid, d1-d14, q3w).

C. HER2 mutation

T-DM1 DRUG

T-DM1(3.6mg/Kg, iv.drip, d1, q3w)

Also known as: Trastuzumab Emtansine

D. HER2 downstream mutation

Everolimus DRUG

Everolimus (4mg, po, qd)

Also known as: RAD001

D. HER2 downstream mutation

CDK4/6 inhibitor DRUG

Palbociclib (125mg, po, qd)

Also known as: Palbociclib；

E. Hormone receptor pathway activation

AI DRUG

Letrozole (2.5mg, qd).

Also known as: Letrozole

E. Hormone receptor pathway activation

Anti-PD-1 monoclonal antibody DRUG

Cindilimab (200mg, iv.drip, d1, q3w)

Also known as: Sintilimab

F. Immune activation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old;
• Women;
• ECOG score 0-2;
• Locally advanced or metastatic breast cancer confirmed by histopathology;
• Positive HER2 expression in cancer tissues (IHC 3 +, or IHC 2 + but FISH amplification);
• Resistant to trastuzumab (including disease progression during or after withdrawal of trastuzumab);
• There were enough specimens for immunohistochemistry, gene detection and establishment of PDO model;
• Hematology and liver and kidney function were normal within 2 weeks before treatment;
• Imaging examination showed measurable lesions (according to RECIST v1.1);
• Women of childbearing age agree to contraception or take contraceptive measures;
• Be able to understand the research program and participate voluntarily.

You may not qualify if:

• Symptomatic, untreated or progressive central nervous system metastases;
• Severe heart disease (poor cardiac function);
• Within 5 years, there was a history of other malignant tumors other than breast cancer;
• In this study, chemotherapy, radiotherapy, immunotherapy or surgery were performed within 3 weeks before the first treatment;
• Patients who are pregnant or lactating, or plan to become pregnant during enrollment.

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead

Study Sites (2)

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, Shaanxi, 710000, China

RECRUITING

Jin Yang

Xi'an, Shaanxi, 710061, China

RECRUITING

MeSH Terms

Interventions

Trastuzumab; pertuzumab; Taxes; Albumin-Bound Paclitaxel; pyrotinib; Capecitabine; Ado-Trastuzumab Emtansine; Everolimus; palbociclib; Letrozole; spartalizumab; sintilimab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Maytansine; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Sirolimus; Nitriles; Triazoles; Azoles

Study Officials

• Jin Yang, Doctor

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jin Yang, Doctor

CONTACT

+862985323473; 792171443@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2021
• First Posted: June 23, 2022
• Study Start: January 1, 2021
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2024
• Last Updated: June 23, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)