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Comparing the Efficacy of Nab-PH+Pyrrolitinib and TCbHP in the Neoadjuvant Treatment of HER2 Positive BC

Primary Purpose

Breast Cancer, HER2-positive Breast Cancer

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Albumin paclitaxel+trastuzumab+pyrrolitinib
Docetaxel+Carboplatin+trastuzumab+Parstuzumab
Sponsored by
Henan Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring HER2-positive Breast Cancer, pathologic complete response, Pyrrolitinib, Disease-free survival

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Age: 18-65 years old, ECOG 0-1 point. Clinical T2-T4d, or T1c with axillary LN+. HER2+, invasive breast cancer confirmed by histopathology;(HER2 positive expression means that there is at least one case of tumor cell immunohistochemical staining intensity of 3+or positive confirmed by fluorescence in situ hybridization [FISH] in the pathological test/review of the primary focus conducted by the Pathology Department of the Research Center Hospital). Having clinically measurable lesions: measurable lesions displayed on ultrasound, mammography, or MR (optional) within the first month of randomization. Organ and bone marrow function tests within one month before chemotherapy indicate no contraindications to chemotherapy:Absolute value of neutrophil count ≥ 2.0 × 109/L; Hemoglobin ≥ 90g/L; Platelet count ≥ 100 × 109/L;Total bilirubin<1.5 ULN (upper limit of normal value); Creatinine<1.5 × ULN; AST/ALT < 1.5 × ULN. Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 55%). Women of childbearing age tested negative for serum pregnancy test 14 days before randomization. Sign an informed consent form. Exclusion Criteria: Stage IV (metastatic) breast cancer. Has received chemotherapy, endocrine therapy, targeted therapy, reflex therapy, etc. for this disease. The patient has a second primary malignant tumor, except for fully treated skin cancer. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures. Serious heart disease or discomfort, including but not limited to the following diseases:Confirmed history of heart failure or systolic dysfunction (LVEF<50%); High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100 bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block; Angina pectoris requiring treatment with anti angina drugs; Clinically significant heart valve disease; ECG shows transmural myocardial infarction; Poor control of hypertension (systolic blood pressure>180 mmHg and/or diastolic blood pressure>100 mmHg). Due to serious and uncontrollable other medical diseases, researchers believe that there are contraindications to chemotherapy. Individuals with a known history of allergies to the drug components of this protocol; Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.

Sites / Locations

  • Henan cancer hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nab-PH+pyrrolitinib regimen group

TCbHP regimen group

Arm Description

Drug dose of Nab PH+pyrrolitinib scheme: albumin paclitaxel 260mg/m 2+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+pyrrolitinib (400mg, QD), one cycle every 21 days.

The drug dose of TCbHP protocol: docetaxel 75 mg/m2+carboplatin (AUC=6)+trastuzumab (initial load dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+patuzumab (initial load dose 840mg, sequential maintenance dose 420 mg), one cycle every 21 days.

Outcomes

Primary Outcome Measures

Pathological complete response rate (pCR rate)
After neoadjuvant chemotherapy and surgery, the resected specimen (breast + axilla) was free of any invasive cancer (ie, ypT0/is, ypN0)

Secondary Outcome Measures

Event-Free Survival (EFS)
EFS was defined as the time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or death from any cause.
DFS
Disease-free Survival,From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause
Distant Disease Free Survival (DDFS)
DDFS is defined as the time from surgery to distant recurrence or death from any cause
Objective Response Rate (ORR)
ORR is defined as the number of target lesion responders as assessed by MRI
number of adverse events
Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 5.0

Full Information

First Posted
June 11, 2023
Last Updated
June 23, 2023
Sponsor
Henan Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05918328
Brief Title
Comparing the Efficacy of Nab-PH+Pyrrolitinib and TCbHP in the Neoadjuvant Treatment of HER2 Positive BC
Official Title
A Non Inferior, Randomized Controlled Phase II Clinical Study Comparing the Efficacy of Nab-PH+Pyrrolitinib and TCbHP in the Neoadjuvant Treatment of HER2 Positive Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 3, 2023 (Actual)
Primary Completion Date
May 3, 2025 (Anticipated)
Study Completion Date
May 3, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Henan Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
At present, the incidence rate of breast cancer has exceeded that of lung cancer, becoming the largest cancer in the world. HER2 overexpression breast cancer accounts for about 20%~30% of all breast cancer patients. HER2 is an important prognostic indicator and therapeutic target for breast cancer. Targeted therapy for HER2 protein is the core treatment of this type of breast cancer. Previous studies have confirmed that TKI drugs can reverse the resistance of large molecule monoclonal antibodies to a certain extent; Moreover, due to the complementarity of therapeutic targets, monoclonal antibodies are associated with TKI Drugs have synergistic effects. TCbHP is one of the preferred neoadjuvant chemotherapy schemes recommended by NCCN guidelines for HER2 positive breast cancer, but its incidence of adverse reactions such as vomiting, diarrhea, anemia, thrombocytopenia is significantly higher than that of the scheme without platinum. In the GeparOcto study and Geparsixto study, based on anthracycline+purple shirt+double target, the addition of carboplatin did not further improve the PCR rate of HER2 positive breast cancer neoadjuvant therapy. GeparSepto research showed that compared to the solvent based paclitaxel group, albumin paclitaxel increased the pCR rate by 8.2% and the IDFS by 7.3%. In the CA024 study, compared to docetaxel, albumin paclitaxel also significantly increased ORR and PFS. In the study by Lavasani SM et al., the neoadjuvant therapy of albumin paclitaxel combined with topiramate achieved a PCR rate of 64%. Therefore, we assume that the new adjuvant treatment scheme of Nab PH+pyrrolitinib can not be inferior to the efficacy of TCbHP, and has a lower incidence of adverse reactions, which may become a new adjuvant treatment option for HER2 positive breast cancer patients.
Detailed Description
At present, the incidence rate of breast cancer has exceeded that of lung cancer, becoming the largest cancer in the world. HER2 overexpression breast cancer accounts for about 20%~30% of all breast cancer patients. HER2 is an important prognostic indicator and therapeutic target for breast cancer. Targeted therapy for HER2 protein is the core treatment of this type of breast cancer. Previous studies have confirmed that TKI drugs can reverse the resistance of large molecule monoclonal antibodies to a certain extent; Moreover, due to the complementarity of therapeutic targets, monoclonal antibodies are associated with TKI Drugs have synergistic effects. TCbHP is one of the preferred neoadjuvant chemotherapy schemes recommended by NCCN guidelines for HER2 positive breast cancer, but its incidence of adverse reactions such as vomiting, diarrhea, anemia, thrombocytopenia is significantly higher than that of the scheme without platinum. In the GeparOcto study and Geparsixto study, based on anthracycline+purple shirt+double target, the addition of carboplatin did not further improve the PCR rate of HER2 positive breast cancer neoadjuvant therapy. GeparSepto research showed that compared to the solvent based paclitaxel group, albumin paclitaxel increased the pCR rate by 8.2% and the IDFS by 7.3%. In the CA024 study, compared to docetaxel, albumin paclitaxel also significantly increased ORR and PFS. In the study by Lavasani SM et al., the neoadjuvant therapy of albumin paclitaxel combined with topiramate achieved a PCR rate of 64%. Therefore, we assume that the new adjuvant treatment scheme of Nab PH+pyrrolitinib can not be inferior to the efficacy of TCbHP, and has a lower incidence of adverse reactions, which may become a new adjuvant treatment option for HER2 positive breast cancer patients. This study aims to explore the efficacy and safety of TCbHP * 6 and Nab-PH+pyrrolitinib * 6 as two new adjuvant treatment regimens in HER2 positive patients through a randomized controlled trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, HER2-positive Breast Cancer
Keywords
HER2-positive Breast Cancer, pathologic complete response, Pyrrolitinib, Disease-free survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Patients who meet the inclusion criteria were randomly divided into TCbHP group and Nab-PH+pyrrolitinib group in a 1:1 ratio.
Masking
None (Open Label)
Masking Description
Non
Allocation
Randomized
Enrollment
610 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nab-PH+pyrrolitinib regimen group
Arm Type
Experimental
Arm Description
Drug dose of Nab PH+pyrrolitinib scheme: albumin paclitaxel 260mg/m 2+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+pyrrolitinib (400mg, QD), one cycle every 21 days.
Arm Title
TCbHP regimen group
Arm Type
Placebo Comparator
Arm Description
The drug dose of TCbHP protocol: docetaxel 75 mg/m2+carboplatin (AUC=6)+trastuzumab (initial load dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+patuzumab (initial load dose 840mg, sequential maintenance dose 420 mg), one cycle every 21 days.
Intervention Type
Drug
Intervention Name(s)
Albumin paclitaxel+trastuzumab+pyrrolitinib
Other Intervention Name(s)
Nab-PH+pyrrolitinib regimen
Intervention Description
Albumin paclitaxel 260mg/m 2+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+pyrrolitinib (400mg, QD), one cycle every 21 days.
Intervention Type
Drug
Intervention Name(s)
Docetaxel+Carboplatin+trastuzumab+Parstuzumab
Other Intervention Name(s)
TCbHP regimen
Intervention Description
Docetaxel 75 mg/m2+carboplatin (AUC=6)+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg)+patuzumab (initial loading dose 840mg, sequential maintenance dose 420 mg), one cycle every 21 days
Primary Outcome Measure Information:
Title
Pathological complete response rate (pCR rate)
Description
After neoadjuvant chemotherapy and surgery, the resected specimen (breast + axilla) was free of any invasive cancer (ie, ypT0/is, ypN0)
Time Frame
immediately after the intervention
Secondary Outcome Measure Information:
Title
Event-Free Survival (EFS)
Description
EFS was defined as the time from randomization to any of the following events: disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or death from any cause.
Time Frame
5-10 years after surgery
Title
DFS
Description
Disease-free Survival,From the date of surgery to the first local, regional, contralateral or distant recurrence, and death from any cause
Time Frame
5-10 years after surgery
Title
Distant Disease Free Survival (DDFS)
Description
DDFS is defined as the time from surgery to distant recurrence or death from any cause
Time Frame
5-10 years after surgery
Title
Objective Response Rate (ORR)
Description
ORR is defined as the number of target lesion responders as assessed by MRI
Time Frame
Preoperative
Title
number of adverse events
Description
Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 5.0
Time Frame
during each cycle of chemotherapy (21 days as 1 cycle)
Other Pre-specified Outcome Measures:
Title
Multiple gene testing
Description
Exploring Multiple Gene Prediction Models for PCR Influencing Different Neoadjuvant Therapy Schemes
Time Frame
immediately after surgery

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age: 18-65 years old, ECOG 0-1 point. Clinical T2-T4d, or T1c with axillary LN+. HER2+, invasive breast cancer confirmed by histopathology;(HER2 positive expression means that there is at least one case of tumor cell immunohistochemical staining intensity of 3+or positive confirmed by fluorescence in situ hybridization [FISH] in the pathological test/review of the primary focus conducted by the Pathology Department of the Research Center Hospital). Having clinically measurable lesions: measurable lesions displayed on ultrasound, mammography, or MR (optional) within the first month of randomization. Organ and bone marrow function tests within one month before chemotherapy indicate no contraindications to chemotherapy:Absolute value of neutrophil count ≥ 2.0 × 109/L; Hemoglobin ≥ 90g/L; Platelet count ≥ 100 × 109/L;Total bilirubin<1.5 ULN (upper limit of normal value); Creatinine<1.5 × ULN; AST/ALT < 1.5 × ULN. Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 55%). Women of childbearing age tested negative for serum pregnancy test 14 days before randomization. Sign an informed consent form. Exclusion Criteria: Stage IV (metastatic) breast cancer. Has received chemotherapy, endocrine therapy, targeted therapy, reflex therapy, etc. for this disease. The patient has a second primary malignant tumor, except for fully treated skin cancer. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures. Serious heart disease or discomfort, including but not limited to the following diseases:Confirmed history of heart failure or systolic dysfunction (LVEF<50%); High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate>100 bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block; Angina pectoris requiring treatment with anti angina drugs; Clinically significant heart valve disease; ECG shows transmural myocardial infarction; Poor control of hypertension (systolic blood pressure>180 mmHg and/or diastolic blood pressure>100 mmHg). Due to serious and uncontrollable other medical diseases, researchers believe that there are contraindications to chemotherapy. Individuals with a known history of allergies to the drug components of this protocol; Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zhenzhen Liu
Organizational Affiliation
Study Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henan cancer hospital
City
Zhengzhou
State/Province
Henan
Country
China

12. IPD Sharing Statement

Learn more about this trial

Comparing the Efficacy of Nab-PH+Pyrrolitinib and TCbHP in the Neoadjuvant Treatment of HER2 Positive BC

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