Breast NeoplasmsPhase 2NCT04983121

Efficacy and Safety of Pyrotinib Maleate Combined With ARX788 Neoadjuvant Treatment in Breast Cancer Patients

A Phase 2 study testing Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788) in people with Breast Neoplasms, run by Shengjing Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 75 years, women only
Conditions the study is for: Breast Neoplasms
What is being tested?: Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 1 siteChina
Study dates: 1 Aug 2021to 15 Aug 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

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 75 years
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

Female patients aged ≥ 18 but ≤ 75 years (The maximal age of the subjects enrolled in the Phase 3 study of pyrotinib is 75 years old, and there is no safety data for the use of the drug in older people);
Diagnosis of breast cancer meets the following criteria: Histologically confirmed invasive breast cancer; Tumor staging: Stage II-III patients who meet the 8th edition of AJCC Cancer Staging Manual; Patients who have undergone neoadjuvant therapy with trastuzumab and pertuzumab and have been assessed as SD (an increase of 0-20%), PD, inoperable or failing to meet the breast-conserving requirements; Failing to meet the breast-conserving requirements is defined as not meeting the following criteria: tumor size of T1 and T2 stage, proper breast volume, proper tumor-to-breast volume ratio, and able to maintain a good breast shape after surgery.
HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC3+) or FISH+;
Eastern Cooperative Oncology Group (ECOG) level 0-1;
The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×109/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×109/L (with no correct treatment within 7 days ); Hemoglobin (Hb) ≥ 90 g/L (with no correct treatment within 7 days ); Total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; Urea nitrogen and creatinine ≤ 1.5×ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 50%; 12-lead electrocardiogram: QT interval ≤ 480 ms;
Able to receive needle biopsy;
Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.

Who cannot join

Patients who are concurrently receiving other anti-tumor therapy;
Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, non-melanoma skin cancer or other malignant tumors;
Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
Cardiac insufficiency, including but not limited to congestive heart failure, transmural myocardial infarction, angina pectoris requiring medical treatment, clinically significant valvular disease and high-risk arrhythmia, or abnormal QTc in the ECG examination during the screening period (at rest, QTc > 450 ms in male or QTc > 470 ms in female after correction of ECG examination);
Uncontrolled hypertension (at rest, systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg);

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Patients who are suffering severe or uncontrolled systemic diseases, such as unstable or uncompensable respiratory, heart, liver, or kidney diseases, as per the investigator's judgments;
Female patients during pregnancy and lactation, or those who are fertile and positive for baseline pregnancy test or those of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period;
Serious concomitant diseases or other comorbid diseases that will endanger the safety of patients or interfere with the completion of the trial, including but not limited to severe hypertension, severe diabetes mellitus, and active infections that are out of control;
Patients with known allergies to any active ingredients or excipients of ARX788, or with a history of protein drug allergy, a history of specific allergies (asthma, rheumatism, eczematous dermatitis), or a history of other severe allergic reactions, who are unsuitable for ARX788 treatment as per the investigator's judgments;
With a history of interstitial pulmonary disease, drug-induced pulmonary interstitial disease, and radiation pneumonitis that require hormone therapy, or any clinically active pulmonary interstitial disease as suggested by any evidence;
Patients who are currently suffering from keratitis, corneal disease, retinal disease, or active eye infection that require any interventions for the eyes.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Nan Niu, MD contact

8618940256668

niunannancy@163.com

China1 site, 1 recruiting

Shengjing Hospital affiliated to China Medical University
Shenyang, Liaoning, 110004
Nan Niu, MD
Cai-Gang Liu, MD
Recruiting

Other trials in China

About this study

Official title: Efficacy and Safety of Pyrotinib Maleate Combined With ARX788 Neoadjuvant Treatment in Stage II-III HER2-positive Breast Cancer Patients Who Have Poor Outcomes After Treatment With Trastuzumab and Pertuzumab

Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788) is an antibody-conjugated drug. Results from the phase I safety, tolerability and pharmacokinetic trial of ARX788 single drug in Chinese patients with advanced HER2 breast cancer indicated a good safety of the test drug, and responses to anti-tumor therapy were observed in the target dose group. Phase II clinical trial is being carried out gradually. This trial is designed to observe the effectiveness and safety of pyrotinib maleate combined with ARX788 neoadjuvant treatment in stage II-III HER2-positive breast cancer patients experiencing a poor efficacy of trastuzumab and pertuzumab.

Read the detailed description

This study adopts a single-arm, multi-center, open design. As per the initial plan, 30 stage II-III human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients who have received neoadjuvant therapy containing trastuzumab and pertuzumab and have been assessed as stable disease (SD) during the neoadjuvant treatment (an increase of 0-20%), disease progression (PD), inoperable or failing to meet the breast-conserving requirements will be enrolled to receive pyrotinib combined with Next-generation Site-specific HER2-targeting Antibody-drug Conjugate (ARX788) neoadjuvant therapy. The main purpose of the study is to observe the efficacy and safety of pyrotinib combined with ARX788 neoadjuvant treatment in stage II-III HER2-positive breast cancer.

Conditions: Breast Neoplasms
Being tested: Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)
Keywords: Breast cancer, Pyrotinib, Neoadjuvant treatment
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)Drug
Also called pyrotinib maleate
The subjects who sign an informed consent will enter the treatment period after screening. Each eligible subject will receive pyrotinib, 320 mg once a day, with 21 days as a session, for 6 sessions in total before operation. Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788) will be intravenously injected at a dose of 1.5 mg/kg, once every 3 weeks, with 21 days as a session, for 6 sessions before surgery. Breast MRI and other imaging examinations will be reviewed every 2 sessions to evaluate the curative effect, and the patient's baseline will be defined based on the imaging report at the time of enrollment. If a definite effect (complete response/partial response) is achieved, surgical treatment will be performed within 4 weeks (> 2 weeks) after completion of 6 sessions of neoadjuvant therapy.

Study groups in NCT04983121
Study group	Role	What they receive
combine treatment group	Experimental	This study adopts a single-arm, multi-center, open design. As per the initial plan, 30 stage II-III human epidermal growth factor receptor 2(HER2)-positive breast cancer patients who have received neoadjuvant therapy containing trastuzumab and pertuzumab and have been assessed as stable disease (SD) during the neoadjuvant treatment (an increase of 0-20%), disease progression (PD), inoperable or failing to meet the breast-conserving requirements will be enrolled to receive pyrotinib combined with Next-generation Site-specific HER2-targeting Antibody-drug Conjugate (ARX788) neoadjuvant therapy. The main purpose of the study is to observe the efficacy and safety of pyrotinib combined with ARX788 neoadjuvant treatment in stage II-III HER2-positive breast cancer. Receives: Drug: Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)

What is being measured

The primary outcome is the main question the study is designed to answer.

Residual tumor burden (RCB) classification in grades
Postoperative pathological results will be used to assess the residual tumor area of primary breast tumor (area in mm×mm), the cell density of the residual tumor（cell density in percentages）, the proportion of carcinoma in situ (proportion of carcinoma in percentages), the number of positive lymph nodes and the diameter of largest metastasis with residual nodes (diameter in mm). The RCB class can be estimated from the above five pathological parameters through a network calculation: RCB-0 in grades: pCR; RCB-I in grades: minimal residual tumor; RCB-II: moderate residual tumor; RCB-III in grades: extensive residual tumor.
Measured: At least 3 years since enrollment

Secondary outcomes (5)

Best overall response rate (BORR) in percentage
The proportion of patients who achieve remission at any point during the study.
Measured: At least 3 years since enrollment
Total pathological complete response rate (tpCR) in percentage
The standard for removal of breast and lymph node tumors which means there are no infiltrating cancer cells at the primary breast and axillary lymph nodes, and only intraductal cancer is allowed on the breast.
Measured: At least 3 years since enrollment
Total breast pathological complete remission rate (bpCR) in percentage
The standard for breast and lymph node tumor removal which means that there are only infiltrating cancer cells at the primary breast tumor site.
Measured: At least 3 years since enrollment
Disease-free survival (DFS)
the time from the day of enrollment to the first occurrence of recurrent disease, including second primary malignancies in the non-breast area and breast ductal carcinoma in situ.
Measured: At least 3 years since enrollment
Overall survival (OS)
the time from the random date to death due to any cause.
Measured: At least 3 years since enrollment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Aug 202115 Aug 2027

First posted30 Jul 2021
Study start1 Aug 2021
Primary completion15 Aug 2027 (estimated)
Study completion15 Aug 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
More trials run by Shengjing HospitalThe 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Single Group: single arm study
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04983121
Sponsor's protocol ID: Shengjing-LCG009
Status last verified: Sep 2022
First submitted: 9 Jul 2021
Last updated: 13 Sep 2022
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Interested in taking part?

Nan Niu, MD

8618940256668

niunannancy@163.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Streamlined Geriatric and Oncological Evaluation Based On IC Technology
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RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Neoplasms trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Pyrotinib Maleate Combined With ARX788 Neoadjuvant Treatment in Stage II-III HER2-positive Breast Cancer Patients Who Have Poor Outcomes After Treatment With Trastuzumab and Pertuzumab
ClinicalTrials.gov ID: NCT04983121
Acronym / sponsor ID: Shengjing-LCG009
Conditions: Breast Neoplasms
Keywords: Breast cancer, Pyrotinib, Neoadjuvant treatment
Phase: Phase 2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 30 participants (estimated)
Lead sponsor: Shengjing HospitalUniversity, hospital or other
Study start: 1 Aug 2021 (actual)
Primary completion: 15 Aug 2027 (estimated)
Study completion: 15 Aug 2027 (estimated)
First posted: 30 Jul 2021 (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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Single Group: single arm study

Arm	Type	Receives
combine treatment group	Experimental	Drug: Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)This study adopts a single-arm, multi-center, open design. As per the initial plan, 30 stage II-III human epidermal growth factor receptor 2(HER2)-positive breast cancer patients who have received neoadjuvant therapy containing trastuzumab and pertuzumab and have been assessed as stable disease (SD) during the neoadjuvant treatment (an increase of 0-20%), disease progression (PD), inoperable or failing to meet the breast-conserving requirements will be enrolled to receive pyrotinib combined with Next-generation Site-specific HER2-targeting Antibody-drug Conjugate (ARX788) neoadjuvant therapy. The main purpose of the study is to observe the efficacy and safety of pyrotinib combined with ARX788 neoadjuvant treatment in stage II-III HER2-positive breast cancer.

Who may qualify

Ages: 18 to 75 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Female patients aged ≥ 18 but ≤ 75 years (The maximal age of the subjects enrolled in the Phase 3 study of pyrotinib is 75 years old, and there is no safety data for the use of the drug in older people);
Diagnosis of breast cancer meets the following criteria: Histologically confirmed invasive breast cancer; Tumor staging: Stage II-III patients who meet the 8th edition of AJCC Cancer Staging Manual; Patients who have undergone neoadjuvant therapy with trastuzumab and pertuzumab and have been assessed as SD (an increase of 0-20%), PD, inoperable or failing to meet the breast-conserving requirements; Failing to meet the breast-conserving requirements is defined as not meeting the following criteria: tumor size of T1 and T2 stage, proper breast volume, proper tumor-to-breast volume ratio, and able to maintain a good breast shape after surgery.
HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC3+) or FISH+;
Eastern Cooperative Oncology Group (ECOG) level 0-1;
The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×109/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×109/L (with no correct treatment within 7 days ); Hemoglobin (Hb) ≥ 90 g/L (with no correct treatment within 7 days ); Total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; Urea nitrogen and creatinine ≤ 1.5×ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 50%; 12-lead electrocardiogram: QT interval ≤ 480 ms;

Key exclusion criteria (12 listed)

Patients who are concurrently receiving other anti-tumor therapy;
Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, non-melanoma skin cancer or other malignant tumors;
Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
Cardiac insufficiency, including but not limited to congestive heart failure, transmural myocardial infarction, angina pectoris requiring medical treatment, clinically significant valvular disease and high-risk arrhythmia, or abnormal QTc in the ECG examination during the screening period (at rest, QTc > 450 ms in male or QTc > 470 ms in female after correction of ECG examination);

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
Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788)Also: pyrotinib maleateThe subjects who sign an informed consent will enter the treatment period after screening. Each eligible subject will receive pyrotinib, 320 mg once a day, with 21 days as a session, for 6 sessions in total before operation. Next-generation Site-specific human epidermal growth factor receptor 2 (HER2)-targeting Antibody-drug Conjugate (ARX788) will be intravenously injected at a dose of 1.5 mg/kg, once every 3 weeks, with 21 days as a session, for 6 sessions before surgery. Breast MRI and other imaging examinations will be reviewed every 2 sessions to evaluate the curative effect, and the patient's baseline will be defined based on the imaging report at the time of enrollment. If a definite effect (complete response/partial response) is achieved, surgical treatment will be performed within 4 weeks (> 2 weeks) after completion of 6 sessions of neoadjuvant therapy.	Drug	combine treatment group

Primary outcome

Residual tumor burden (RCB) classification in grades
Time frame: At least 3 years since enrollment
Postoperative pathological results will be used to assess the residual tumor area of primary breast tumor (area in mm×mm), the cell density of the residual tumor（cell density in percentages）, the proportion of carcinoma in situ (proportion of carcinoma in percentages), the number of positive lymph nodes and the diameter of largest metastasis with residual nodes (diameter in mm). The RCB class can be estimated from the above five pathological parameters through a network calculation: RCB-0 in grades: pCR; RCB-I in grades: minimal residual tumor; RCB-II: moderate residual tumor; RCB-III in grades: extensive residual tumor.

5 secondary outcomes

Best overall response rate (BORR) in percentage
Time frame: At least 3 years since enrollment
Total pathological complete response rate (tpCR) in percentage
Time frame: At least 3 years since enrollment
Total breast pathological complete remission rate (bpCR) in percentage
Time frame: At least 3 years since enrollment
Disease-free survival (DFS)
Time frame: At least 3 years since enrollment
Overall survival (OS)
Time frame: At least 3 years since enrollment

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2022.
Individual participant dataSharing planned: No

Related trials for Breast Neoplasms

Active, not recruiting
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Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
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Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
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RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

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.

Nan Niu, MD contact

8618940256668

niunannancy@163.com

Cai-Gang Liu principal investigator

Department of Breast Surgery, Shengjing Hospital affiliated to China Medical University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 7 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Nan Niu, MD (8618940256668, niunannancy@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Residual tumor burden (RCB) classification in grades (time frame: At least 3 years since enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04983121.

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 13 Sep 2022.