HER2+ Breast CancerPhase 3NCT05429684
Precise Therapy for Refractory HER2 Positive Advanced Breast Cancer
A Phase 3 study testing Trastuzumab, Pertuzumab and Nab paclitaxel in people with HER2+ Breast Cancer, run by First Affiliated Hospital Xi'an Jiaotong University at 2 sites in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- HER2+ Breast Cancer
- What is being tested?
- Trastuzumab, Pertuzumab and Nab paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 2 sitesChina
- Study dates
- 1 Jan 2021to 28 Feb 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-70 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);
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- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, 710000
Jin Yang, PhD, 0086-18991232383, 1473106133@qq.com
- Recruiting
Jin Yang
Xi'an, Shaanxi, 710061
Jin Yang, +862985324600, 1473106133@qq.com
About this study
Official title: 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.
Read the 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.
- Conditions
- HER2+ Breast Cancer
- Being tested
- Trastuzumab, Pertuzumab, Nab paclitaxel, Pyrotinib, Capecitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called herceptin；Inetetamab
Trastuzumab (6mg/Kg, iv.drip, d1, q3w)
PertuzumabDrug
Also called Perjeta
Patuzumab (420mg iv.drip, d1,q3w)
Nab paclitaxelDrug
Also called Abraxane
nab-paclitaxel (200mg iv.drip, d1,d8, q3w)
PyrotinibDrug
Also called SHR-1258
Pyroltinib (400mg po qd)
CapecitabineDrug
Capecitabine (1250mg/m2, po, bid, d1-d14, q3w).
T-DM1Drug
Also called Trastuzumab Emtansine
T-DM1(3.6mg/Kg, iv.drip, d1, q3w)
EverolimusDrug
Also called RAD001
Everolimus (4mg, po, qd)
CDK4/6 inhibitorDrug
Also called Palbociclib；
Palbociclib (125mg, po, qd)
AIDrug
Also called Letrozole
Letrozole (2.5mg, qd).
Anti-PD-1 monoclonal antibodyDrug
Also called Sintilimab
Cindilimab (200mg, iv.drip, d1, q3w)
| Study group | Role | What they receive |
|---|---|---|
| A. HER2 low expression | Experimental | Phenotype was signatured by HER2 low expression. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab paclitaxel |
| B. HER2 amplified | Experimental | Signatured by wild type HER2 amplified. Receives: Drug: Trastuzumab; Drug: Pertuzumab; Drug: Nab paclitaxel |
| C. HER2 mutation | Experimental | Signatured by HER2 mutation. Receives: Drug: Pyrotinib; Drug: Capecitabine |
| D. HER2 downstream mutation | Experimental | Signatured by HER2 downstream mutation of PI3KCA, TP53 or PTEN. Receives: 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. Receives: Drug: Trastuzumab; Drug: CDK4/6 inhibitor; Drug: AI |
| F. Immune activation | Experimental | Signatured by high TMB or PD-L1 positively expressed. Receives: Drug: Trastuzumab; Drug: Anti-PD-1 monoclonal antibody |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
objective response rate (ORR) according to RECIST (version 1.1) of each group
Measured: Up to six weeks, first evaluation
PDO model inhibition rate
Tumor regression rate based on the calculation of the long diameter in each group
Measured: during the procedure
Secondary outcomes (1)
PFS1
Progress free survival (PFS) according to RECIST (version 1.1) of each group
Measured: during the procedure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2022
- Study start1 Jan 2021
- Primary completion28 Feb 2024 (estimated)
- Study completion28 Feb 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HER2+ Breast CancerStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jin Yang, Doctor, Principal investigator, First Affiliated Hospital Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05429684
- Sponsor's protocol ID
- XJTU1AF-CRF-2020-006
- Status last verified
- May 2022
- First submitted
- 12 Dec 2021
- Last updated
- 23 Jun 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precise Targeted Therapy for Refractory HER2 Positive Advanced Breast Cancer Based on Genome Signature and Drug Sensitivity of PDO Model
- ClinicalTrials.gov ID
- NCT05429684
- Acronym / sponsor ID
- XJTU1AF-CRF-2020-006
- Conditions
- HER2+ Breast Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 28 Feb 2024 (estimated)
- Study completion
- 28 Feb 2024 (estimated)
- First posted
- 23 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| A. HER2 low expression | Experimental | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Nab paclitaxelPhenotype was signatured by HER2 low expression. |
| B. HER2 amplified | Experimental | Drug: Trastuzumab, Drug: Pertuzumab, Drug: Nab paclitaxelSignatured by wild type HER2 amplified. |
| C. HER2 mutation | Experimental | Drug: Pyrotinib, Drug: CapecitabineSignatured by HER2 mutation. |
| D. HER2 downstream mutation | Experimental | Drug: Trastuzumab, Drug: Nab paclitaxel, Drug: T-DM1, Drug: EverolimusSignatured by HER2 downstream mutation of PI3KCA, TP53 or PTEN. |
| E. Hormone receptor pathway activation | Experimental | Drug: Trastuzumab, Drug: CDK4/6 inhibitor, Drug: AISignatured by both ER and PR strongly expressed,or CCND1 amplified. |
| F. Immune activation | Experimental | Drug: Trastuzumab, Drug: Anti-PD-1 monoclonal antibodySignatured by high TMB or PD-L1 positively expressed. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 18-70 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);
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabAlso: herceptin；InetetamabTrastuzumab (6mg/Kg, iv.drip, d1, q3w) | Drug | A. HER2 low expression, B. HER2 amplified, D. HER2 downstream mutation, E. Hormone receptor pathway activation, F. Immune activation |
| PertuzumabAlso: PerjetaPatuzumab (420mg iv.drip, d1,q3w) | Drug | A. HER2 low expression, B. HER2 amplified |
| Nab paclitaxelAlso: Abraxanenab-paclitaxel (200mg iv.drip, d1,d8, q3w) | Drug | A. HER2 low expression, B. HER2 amplified, D. HER2 downstream mutation |
| PyrotinibAlso: SHR-1258Pyroltinib (400mg po qd) | Drug | C. HER2 mutation |
| CapecitabineCapecitabine (1250mg/m2, po, bid, d1-d14, q3w). | Drug | C. HER2 mutation |
| T-DM1Also: Trastuzumab EmtansineT-DM1(3.6mg/Kg, iv.drip, d1, q3w) | Drug | D. HER2 downstream mutation |
| EverolimusAlso: RAD001Everolimus (4mg, po, qd) | Drug | D. HER2 downstream mutation |
| CDK4/6 inhibitorAlso: Palbociclib；Palbociclib (125mg, po, qd) | Drug | E. Hormone receptor pathway activation |
| AIAlso: LetrozoleLetrozole (2.5mg, qd). | Drug | E. Hormone receptor pathway activation |
| Anti-PD-1 monoclonal antibodyAlso: SintilimabCindilimab (200mg, iv.drip, d1, q3w) | Drug | F. Immune activation |
Primary outcome
ORR
Time frame: Up to six weeks, first evaluation
objective response rate (ORR) according to RECIST (version 1.1) of each group
PDO model inhibition rate
Time frame: during the procedure
Tumor regression rate based on the calculation of the long diameter in each group
1 secondary outcome
PFS1
Time frame: during the procedure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jin Yang, Doctor principal investigator
First Affiliated Hospital Xi'an Jiaotong University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trastuzumab, Pertuzumab and Nab paclitaxel in people with HER2+ Breast Cancer, run by First Affiliated Hospital Xi'an Jiaotong University at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jin Yang, Doctor (+862985323473, 792171443@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: Up to six weeks, first evaluation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2022.