Pyrotinib as Neoadjuvant Agent for Non-objective Response HER2-positive Early Breast Cancer

NCT ID: NCT04717531

Last Updated: 2021-06-04

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-03
• Study Completion Date: 2024-05-31

Brief Summary

The study assesses the efficacy of neoadjuvant treatment with pyrotinib and trastuzumab with chemotherapy, mainly pathological complete response (pCR) rates in the breast and axilla.

And also assesses side effects, event-free survival (EFS), disease-free survival (DFS), distant disease-free survival (DDFS), and objective response rates (ORR).

Detailed Description

Investigational Medical Products (IMPs) will be pyrotinib (B), trastuzumab (H), pertuzumab (P), docetaxel (T), epirubicin (E), and cyclophosphamide (C).

Magnetic resonance imaging (MRI) will be performed at baseline and 2 cycles after neoadjuvant therapy with trastuzumab, pertuzumab, and docetaxel (THP*2). Non-objective response patients will be randomly assigned (2:1) to receive 2 cycles of pyrotinib and trastuzumab with docetaxel followed by 4 cycles of pyrotinib and epirubicin plus cyclophosphamide (THB*2-ECB[epirubicine, cyclophosphamide, and pyrotinib]*4, cohort A), or 2 cycles of trastuzumab and pertuzumab with docetaxel followed by 4 cycles of epirubicin plus cyclophosphamide (THP*2-EC*4, cohort B).

During the neoadjuvant therapy, the side effects and all the events were recorded and analyzed. After surgery, the efficacy of pCR rate and ORR were analyzed. And long time follow-up will also be performed to analyze EFS, DFS, DDFS, and ORR.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

2 cycles of pyrotinib and trastuzumab with docetaxel followed by 4 cycles of pyrotinib, epirubicin, and cyclophosphamide (THB*2-ECB*4). The cycles repeated every 21 days.

Pyrotinib: 400mg, qd, po, day 1-21; Trastuzumab: 6 mg/kg, day 1; Docetaxel: 100 mg/m2, day 1; Epirubicin: 90 mg/m2, day 1; Cyclophosphamide: 600 mg/m2, day 1.

Group Type: EXPERIMENTAL

Pyrotinib

Intervention Type: DRUG

400mg, qd, po, day 1-21

Trastuzumab

Intervention Type: DRUG

6 mg/kg, day 1

Docetaxel

Intervention Type: DRUG

100 mg/m2, day 1

Epirubicin

Intervention Type: DRUG

90mg/m2, day 1

Cyclophosphamide

Intervention Type: DRUG

600 mg/m2, day 1

Cohort B

2 cycles of trastuzumab and pertuzumab with docetaxel followed by 4 cycles of epirubicin and cyclophosphamide (THP*2-EC*4). The cycles repeated every 21 days.

Trastuzumab: 6 mg/kg, day 1; Pertuzumab: 420 mg, day 1; Docetaxel: 100 mg/m2, day 1; Epirubicin: 90mg/m2, day 1; Cyclophosphamide: 600 mg/m2, day 1.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

6 mg/kg, day 1

Pertuzumab

Intervention Type: DRUG

420 mg, day 1

Docetaxel

Intervention Type: DRUG

100 mg/m2, day 1

Epirubicin

Intervention Type: DRUG

90mg/m2, day 1

Cyclophosphamide

Intervention Type: DRUG

600 mg/m2, day 1

Interventions

Pyrotinib

400mg, qd, po, day 1-21

Intervention Type: DRUG

Trastuzumab

6 mg/kg, day 1

Intervention Type: DRUG

Pertuzumab

420 mg, day 1

Intervention Type: DRUG

Docetaxel

100 mg/m2, day 1

Intervention Type: DRUG

Epirubicin

90mg/m2, day 1

Intervention Type: DRUG

Cyclophosphamide

600 mg/m2, day 1

Intervention Type: DRUG

Other Intervention Names

B; H; P; T; E; C

Eligibility Criteria

Inclusion Criteria

1. Female patients between 18-70 years old. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 3. Histologically confirmed HER2 (human epidermal growth factor receptor-2)-positive invasive breast cancer.

4. Non-objective response after 2 cycles of THP as neoadjuvant treatment. 5. Known hormone receptor status. 6. Patient has adequate bone marrow, liver, and renal function:

1. Hematological: White blood cell (WBC) count > 3.5 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 90 x109/L, and hemoglobin ≥ 90 g/dL.

2. Hepatic function: total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (except for Gilbert's syndrome); aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 times ULN.

3. Renal function: serum creatinine and BUN ≤ 1.5 x ULN, or creatinine clearance ≥ 50 ml/min/1.73 m2 for patients with creatinine levels above institutional normal.

8. LVEF ≥50% measured by echocardiography. 9. Fertile patients must use effective contraception (barrier method - condoms, diaphragm - also in conjunction with spermicidal jelly, or total abstinence. Oral, injectable, or implant hormonal contraceptives are not allowed).

10. Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential).

11. Signed informed consent form (ICF).

Exclusion Criteria

1. Metastatic breast cancer;

2. Previous (less than 10 years) or current history of malignant neoplasms, except for curatively treated: Basal and squamous cell carcinoma of the skin; Carcinoma in situ of the cervix.

3. Patients with a prior malignancy diagnosed more than 10 years prior to randomization may enter the study. Patients must have been curatively treated with surgery alone. Radiation therapy or systemic therapy (chemotherapy or endocrine) are NOT permitted. Prior diagnoses of breast cancer or melanoma are excluded.

4. Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;

5. Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of the need for major surgery within the course of the study treatment.

6. Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension (≥180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen;

7. Known hypersensitivity reaction to one of the investigational compounds or incorporated substances.

8. Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment.

9. Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xiaoming Zha, MD

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Locations

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jue Wang, MD

Role: CONTACT

wangjue200011@njmu.edu.cn

00862568308172

Facility Contacts

Jue Wang, MD

Role: primary

wangjue200011@njmu.edu.cn

00862568308172

Other Identifiers

PYHOPE-BC-104

Identifier Type: -

Identifier Source: org_study_id