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

NCT04717531 | Unknown Phase 2

• 1 other identifier: PYHOPE-BC-104
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Breast Cancer

Keywords

neoadjuvant; pyrotinib; HER2-positive

Outcome Measures

Primary Outcomes (1)

• Pathological complete response (pCR) rate

  Number of patients with pCR (no invasive breast cancer in the breast and axilla)

  up to 30 weeks

Secondary Outcomes (5)

• Number of patients with grade >3 adverse events as a measure of safety and tolerability

  up to 30 weeks

• Objective response rate (ORR)

  up to 30 weeks

• Disease-free Survival (DFS)

  Following surgery, every 12 months until Year 10

• Event Free Survival (EFS)

  From date of randomization until follow-up to 10 years

• Distant-disease- free survival (DDFS)

  From date of randomization until follow-up to 10 years

Study Arms (2)

Cohort A

EXPERIMENTAL

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.

Drug: Pyrotinib; Drug: Trastuzumab; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Cohort B

ACTIVE COMPARATOR

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.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Docetaxel; Drug: Epirubicin; Drug: Cyclophosphamide

Interventions

Pyrotinib DRUG

400mg, qd, po, day 1-21

Also known as: B

Cohort A

Trastuzumab DRUG

6 mg/kg, day 1

Also known as: H

Cohort A; Cohort B

Pertuzumab DRUG

420 mg, day 1

Also known as: P

Cohort B

Docetaxel DRUG

100 mg/m2, day 1

Also known as: T

Cohort A; Cohort B

Epirubicin DRUG

90mg/m2, day 1

Also known as: E

Cohort A; Cohort B

Cyclophosphamide DRUG

600 mg/m2, day 1

Also known as: C

Cohort A; Cohort B

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. 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:
• 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.
• 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.
• 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.
• \. 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).
• \. Negative serum pregnancy test, within 2-weeks (preferably 7 days) prior to randomization (For women of childbearing potential).
• \. Signed informed consent form (ICF).

You may not qualify if:

• Metastatic breast cancer;
• 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.
• 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.
• Concurrent treatment with an investigational agent or participation in another therapeutic clinical trial;
• 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.
• 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;
• Known hypersensitivity reaction to one of the investigational compounds or incorporated substances.
• Pregnant or lactating patients. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Trastuzumab; Protons; pertuzumab; Docetaxel; Epirubicin; Cyclophosphamide

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; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• Xiaoming Zha, MD

  The First Affiliated Hospital with Nanjing Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jue Wang, MD

CONTACT

00862568308172; wangjue200011@njmu.edu.cn

Study Design

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

Study Record Dates

• First Submitted: January 17, 2021
• First Posted: January 22, 2021
• Study Start: June 3, 2021
• Primary Completion: June 1, 2023
• Study Completion: May 31, 2024
• Last Updated: June 4, 2021

Record last verified: 2021-06

Locations

CN (1)