- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05426486
A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients
March 30, 2023 updated by: Caigang Liu
A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Breast Cancer
This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.
Patients will be randomized (1:1) to one of the two treatment arms: arm 1, ARX788 plus pyrotinib maleate for 6 cycles; arm 2, trastuzumab plus pertuzumab with docetaxel and carboplatin for six cycles.
Patients will undergo surgery after neoadjuvant therapy.
Efficacy will be assessed every 2 cycles.
Study Type
Interventional
Enrollment (Anticipated)
150
Phase
- Phase 2
- 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
- Name: Nan Niu, MD
- Phone Number: 86-18940256668
- Email: niunannancy@163.com
Study Locations
-
-
Liaoning
-
Shenyang, Liaoning, China, 110004
- Recruiting
- Shengjing Hospital affiliated to China Medical University
-
Contact:
- Nan Liu, MD
- Phone Number: 86-18940256668
- Email: niunannancy@163.com
-
Principal Investigator:
- Caigang Liu, MD
-
-
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
Ages Eligible for Study
18 years to 75 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- Female patients aged ≥ 18 but ≤ 75 years;
- 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;
- HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC 3+) or IHC 2+ with FISH+;
- Eastern Cooperative Oncology Group (ECOG) level 0-1;
- The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×10^9/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×10^9/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;
- Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.
Exclusion Criteria:
- Previously received any anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
- Patients who are concurrently receiving other anti-tumor therapy;
- Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
- Stage IV breast cancer;
- With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ and melanoma skin cancer;
- Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
- Patients with known allergies to any active ingredients or excipients of Investigational medicinal product;
- 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;
- Once suffered from any heart disease, including: (1) arrhythmia with clinical significance, (2) myocardial infarction; (3) heart failure; (4) investigator's judgment as not suitable for participating in this trial;
- 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;
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: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ARX788 + pyrotinib maleate
ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles
|
HER2 antibody-drug conjugate
EGFR/HER2 dual inhibitor
|
Active Comparator: trastuzumab + pertuzumab + docetaxel + carboplatin
Trastuzumab (8 mg/kg first dose, followed 6 mg/kg) puls pertuzumab (840 mg first dose, followed 420 mg) plus docetaxel (75 mg/m3) plus carboplatin (AUC6) IV every 3 weeks for 6 cycles
|
anti-Her2 monoclonal antibody
Other Names:
anti-HER2 monoclonal antibody
Other Names:
Cytotoxic chemotherapy
Cytotoxic chemotherapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total pathological complete response rate (tpCR) in percentage
Time Frame: 3 years
|
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.
|
3 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total breast pathological complete remission rate (bpCR) in percentage
Time Frame: 3 years
|
The standard for breast and lymph node tumor removal which means that there are only infiltrating cancer cells at the primary breast tumor site.
|
3 years
|
Residual tumor burden (RCB) classification in grades
Time Frame: 3 years
|
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.
|
3 years
|
Best overall response rate (BORR) in percentage
Time Frame: 3 years
|
The proportion of patients who achieve remission at any point during the study.
|
3 years
|
Five-year overall survival (OS)
Time Frame: 5 years
|
The time from the random date to death due to any cause.
|
5 years
|
Disease-free survival (DFS)
Time Frame: 3 years
|
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.
|
3 years
|
Adverse events (AE)
Time Frame: 3 years
|
Adverse events (AE) will be assessed as per the NCI-CTC AE 5.0 standard.
|
3 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Health-related quality of life (HRQOL)
Time Frame: 3 years
|
The European Organization for Research and Treatment-QOL questionnaire and breast cancer specific module (EORTC QLQ-C30 and QLQ-BR23) will use to measure the HRQOL.
Compare each domain scores and global health/quality-of-life score of EORTC QLQ-C30 with baseline, and compare each domain scores of EORTC QLQ-BR23 with baseline.
|
3 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Caigang Liu, MD, Shengjing Hospital
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)
May 23, 2022
Primary Completion (Anticipated)
December 30, 2025
Study Completion (Anticipated)
December 30, 2026
Study Registration Dates
First Submitted
June 12, 2022
First Submitted That Met QC Criteria
June 21, 2022
First Posted (Actual)
June 22, 2022
Study Record Updates
Last Update Posted (Actual)
April 3, 2023
Last Update Submitted That Met QC Criteria
March 30, 2023
Last Verified
March 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MUKDEN 06
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.
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