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

June 2, 2021 updated by: The First Affiliated Hospital with Nanjing Medical University

Pyrotinib as Neoadjuvant Agent for Non-objective Response Patients of HER2-positive Early Breast Cancer Treated by Trastuzumab, Pertuzumab, and Chemotherapy (PYHOPE-BC-104): a Randomized, Controlled, Phase Ⅱ Trial

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China
        • Recruiting
        • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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.
Drug: Pyrotinib
400mg, qd, po, day 1-21
Other Names:
  • B
Drug: Trastuzumab
6 mg/kg, day 1
Other Names:
  • H
Drug: Docetaxel
100 mg/m2, day 1
Other Names:
  • T
Drug: Epirubicin
90mg/m2, day 1
Other Names:
  • E
Drug: Cyclophosphamide
600 mg/m2, day 1
Other Names:
  • C
ACTIVE_COMPARATOR: 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.
Drug: Trastuzumab
6 mg/kg, day 1
Other Names:
  • H
Drug: Docetaxel
100 mg/m2, day 1
Other Names:
  • T
Drug: Epirubicin
90mg/m2, day 1
Other Names:
  • E
Drug: Cyclophosphamide
600 mg/m2, day 1
Other Names:
  • C
Drug: Pertuzumab
420 mg, day 1
Other Names:
  • P

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR) rate
Time Frame: up to 30 weeks
Number of patients with pCR (no invasive breast cancer in the breast and axilla)
up to 30 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with grade >3 adverse events as a measure of safety and tolerability
Time Frame: up to 30 weeks
To describe the safety of the various regimens toxicity is compared between the two arms.
up to 30 weeks
Objective response rate (ORR)
Time Frame: up to 30 weeks
ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
up to 30 weeks
Disease-free Survival (DFS)
Time Frame: Following surgery, every 12 months until Year 10
DFS was defined as the time from surgery to the first date of breast cancer relapse, second primary tumor (including contralateral breast cancer), or death without documented prior relapse. Data will be reported when they are mature and available, likely when a median of 3 years follow up has been reached.
Following surgery, every 12 months until Year 10
Event Free Survival (EFS)
Time Frame: From date of randomization until follow-up to 10 years
EFS will be defined as the time from random assignment to documentation of the first of the following events: discontinuation of study therapy due to protocol-defined progression prior to surgery; local, regional, or distant recurrence of breast cancer following curative surgery; a new breast cancer; another new onset malignancy; or death as a result of any cause.
From date of randomization until follow-up to 10 years
Distant-disease- free survival (DDFS)
Time Frame: From date of randomization until follow-up to 10 years
DDFS is defined as the time period from randomization to the first event.
From date of randomization until follow-up to 10 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Investigators

  • Principal Investigator: Xiaoming Zha, MD, The First Affiliated Hospital with Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 3, 2021

Primary Completion (ANTICIPATED)

June 1, 2023

Study Completion (ANTICIPATED)

May 31, 2024

Study Registration Dates

First Submitted

January 17, 2021

First Submitted That Met QC Criteria

January 19, 2021

First Posted (ACTUAL)

January 22, 2021

Study Record Updates

Last Update Posted (ACTUAL)

June 4, 2021

Last Update Submitted That Met QC Criteria

June 2, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PYHOPE-BC-104

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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