Trastuzumab Combined With Pertuzumab for Adjuvant Treatment of Breast Cancer After Neoadjuvant Therapy

NCT04973319 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: Shengjing-LCG008
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with HER-2 positive breast cancer who have poor outcomes after endocrinotherapy and standard chemotherapy can be significantly improved by the use of anti-HER-2 monoclonal antibody trastuzumab. In the current clinical practice of neoadjuvant therapy, trastuzumab combined with chemotherapy can significantly increase the pCR and improve the outcomes in patients. However, there seems to be no available treatment for patients who have no pCR and still have residual tumors except for sequential trastuzumab treatment for 1 year. Compared with trastuzumab, a HER-2 macromolecule inhibitor, pyrotinib has a different site of action and an increased EGFR target. Compared with lapatinib, a small molecule inhibitor of EGFR and HER-2, pyrotinib is an irreversible inhibitor, with the ability to achieve a better curative effect at a lower human plasma exposure level. This trial is designed to evaluate the effectiveness and safety of trastuzumab combined with pertuzumab followed by sequential pyrotinib treatment in non-pCR patients after neoadjuvant therapy.

Conditions

Breast Cancer

Keywords

breast cancer; pyrotinib; trastuzumab; pertuzumab

Outcome Measures

Primary Outcomes (1)

• Invasive Disease-Free Survival (IDFS)

  the time from the date of randomization to the first appearance of recurrent disease. Recurrent diseases include ipsilateral or contralateral breast cancer, local or regional recurrence, distant recurrence and death from any cause.

  at least 3 years from the beginning of randomization.

Secondary Outcomes (3)

• Disease-Free Survival (DFS)

  at least 3 years from the date of randomization

• overall survival (OS)

  at least 3 years from the date of randomization

• Distant Disease-Free Survival (DDFS)

  at least 3 years from the date of randomization

Other Outcomes (1)

• Adverse event (AE)

  from the date of randomization to no more than 28 days after the last drug withdrawal.

Study Arms (2)

test group

EXPERIMENTAL

Each subject in the test group will receive the test drug (pyrotinib) for 52 weeks, and will be followed up for at least 3 years from the start of randomization, until disease recurrence, intolerable toxicity, withdrawal of informed consent, or termination of the medication as per the investigator's judgment. The subject who has a second primary malignant tumor in a non-breast area will continue to be followed up until a recurrent disease or death due to primary breast cancer. The subjects who are hormone receptor-positive will be advised to receive endocrinotherapy simultaneously. Within 28 days after the last administration of the test drug, the subjects in the test group must complete the safety follow-up and the end-of-treatment visit and continue to receive the follow-up visit.

Drug: Pyrotinib

control group

OTHER

Each enrolled subject will complete at least ≥ 24 weeks (8 drug delivery cycles) of trastuzumab combined with pertuzumab in the neoadjuvant and/or adjuvant treatment phase.

Drug: Trastuzumab

Interventions

Pyrotinib DRUG

Each subject in the test group will receive the test drug (pyrotinib) for 52 weeks, and will be followed up for at least 3 years from the start of randomization, until disease recurrence, intolerable toxicity, withdrawal of informed consent, or termination of the medication as per the investigator's judgment.

Also known as: Trastuzumab and pertuzumab

test group

Trastuzumab DRUG

Each enrolled subject will complete at least ≥ 24 weeks (8 drug delivery cycles) of trastuzumab combined with pertuzumab in the neoadjuvant and/or adjuvant treatment phase.

Also known as: pertuzumab

control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• ECOG level 0-1;
• Primary infiltrating breast lesions and lymph nodes should follow these conditions at the same time: histologically confirmed invasive breast cancer; receiving neoadjuvant treatment and completing the operation, with postoperative pathological examination indicating residual invasive cancer in the breast or axillary lymph nodes; HER2-positive breast cancer is confirmed in the pathology test, with 3+ in immunohistochemistry (IHC) test and HER2 gene amplification (HER2/CEP17 ≥ 2.0 or average HER2 copy number/cell number ≥ 6); no recurrent and metastatic disease after surgery;
• HER-2 positive breast cancer patients who have non-pCR after trastuzumab+pertuzumab as neoadjuvant therapy, and have completed trastuzumab combined with pertuzumab as adjuvant treatment. During the neoadjuvant and/or adjuvant therapy phase, at least ≥24 weeks (8 drug delivery cycles) of trastuzumab + pertuzumab. And the time interval from the end of the last trastuzumab treatment to entering the trial must be ≤ 1 year;
• Hormone receptor status (ER and PR) that is known;
• The functional level of major organs must conform to the following requirements (no blood transfusion, no use of white blood cell- and platelet-increasing drugs within 2 weeks before screening): Neutrophils (ANC) ≥ 1.5×109/L; Platelet count (PLT) ≥ 90×109/L; Hemoglobin (Hb) ≥ 90 g/L; Total bilirubin (TBIL)≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5×ULN;
• Female patients who are not menopausal or not surgically sterilized agree to abstain from sex or use effective non-hormonal drugs for contraception during the treatment period and within 8 weeks after the last administration;
• Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.

You may not qualify if:

• With a history of recurrent local or regional breast disease;
• Stage IV (metastatic) breast cancer;
• Bilateral breast cancer;
• With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or squamous cell carcinoma;
• Patients who have received pyrotinib, lapatinib, neratinib or other tyrosine kinase inhibitors, enmetrastuzumab (T-DM1), and other anti-tumor biological therapies or tumor immunotherapy;
• Patients who are receiving anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy;
• Severe heart disease or discomfort, including but not limited to the following diseases: a confirmed history of heart failure or systolic dysfunction (LVEF \< 50%); high-risk uncontrolled arrhythmia, such as atrial tachycardia, remarkable ventricular arrhythmia (such as ventricular tachycardia) or higher-grade atrioventricular block; angina pectoris requiring anti-angina medication; clinically significant valvular disease; transmural myocardial infarction shown by ECG; uncontrolled blood pressure in patients with hypertension who have been given antihypertensive drugs (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg);
• Inability to swallow, intestinal obstruction or other factors that affect drug taking and absorption;
• With a history of diagnosed neurological or mental disorders, including involuntary behavior or mental illness;
• With a history of gastrointestinal diseases with diarrhea as the main symptom;
• Patients who are known to have a history of allergies to the drug components in this trial; have a history of immunodeficiency, including HIV positive results, or other acquired or congenital immunodeficiency diseases; or have a history of organ transplantation;
• Female patients during pregnancy and lactation, or those who are fertile and positive for baseline pregnancy test;
• Serious concomitant diseases or other comorbid diseases that will interfere with the planned treatment, including infectious diseases with active infections (including but not limited to hepatitis B, active hepatitis C, active tuberculosis, active syphilis, etc.); or any other cases in which the investigator believes that the patient cannot participate in the trial.

Sponsors & Collaborators

• Shengjing Hospital: lead

Study Sites (1)

Shengjing Hospital affiliated to China Medical University

Shenyang, Liaoning, 110004, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cai-Gang Liu, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nan Niu, MD

CONTACT

8618940256668; niunannancy@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Model Details: Participants are assigned to one of two or more groups in parallel for the duration of the study.

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 22, 2021
• Study Start: August 1, 2021
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: July 22, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)