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

NCT05918328 | Recruiting Phase 2 DMC

• 1 other identifier: HELEN-013
• Study Type: interventional
• Target: 610
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; HER2-positive Breast Cancer

Keywords

HER2-positive Breast Cancer; pathologic complete response; Pyrrolitinib; Disease-free survival

Outcome Measures

Primary Outcomes (1)

• 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)

  immediately after the intervention

Secondary Outcomes (5)

• Event-Free Survival (EFS)

  5-10 years after surgery

• DFS

  5-10 years after surgery

• Distant Disease Free Survival (DDFS)

  5-10 years after surgery

• Objective Response Rate (ORR)

  Preoperative

• number of adverse events

  during each cycle of chemotherapy (21 days as 1 cycle)

Other Outcomes (1)

• Multiple gene testing

  immediately after surgery

Study Arms (2)

Nab-PH+pyrrolitinib regimen group

EXPERIMENTAL

Drug dose of Nab PH+pyrrolitinib scheme: albumin paclitaxel （260mg/㎡ every 3 weeks or 125mg/㎡ weekly）+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg, once every 3 weeks)+pyrrolitinib (320mg, QD), 3 weeks as one cycle.

Drug: Albumin paclitaxel+trastuzumab+pyrrolitinib

TCbHP regimen group

PLACEBO COMPARATOR

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.

Drug: Docetaxel+Carboplatin+trastuzumab+Parstuzumab

Interventions

Albumin paclitaxel+trastuzumab+pyrrolitinib DRUG

albumin paclitaxel （260mg/㎡ every 3 weeks or 125mg/㎡ weekly）+trastuzumab (initial loading dose 8 mg/kg, sequential maintenance dose 6 mg/kg, once every 3 weeks)+pyrrolitinib (320mg, QD), 3 weeks as one cycle.

Also known as: Nab-PH+pyrrolitinib regimen

Nab-PH+pyrrolitinib regimen group

Docetaxel+Carboplatin+trastuzumab+Parstuzumab DRUG

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

Also known as: TCbHP regimen

TCbHP regimen group

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan cancer hospital

Zhengzhou, Henan, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Pathologic Complete Response

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Zhenzhen Liu

  Study Principal Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenzhen Liu

CONTACT

13603862755; liuzhenzhen73@126.com

Dechuang Jiao

CONTACT

13598004327; jiaodechuang@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Non
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Patients who meet the inclusion criteria were randomly divided into TCbHP group and Nab-PH+pyrrolitinib group in a 1:1 ratio.

Study Record Dates

• First Submitted: June 11, 2023
• First Posted: June 26, 2023
• Study Start: May 3, 2023
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 7, 2025

Record last verified: 2024-11

Locations

CN (1)