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

Primary Purpose

Breast Cancer

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Pyrotinib

Trastuzumab

Pertuzumab

Docetaxel

Epirubicin

Cyclophosphamide

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring neoadjuvant, pyrotinib, HER2-positive

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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:

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.

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:

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.

Sites / Locations

the First Affiliated Hospital of Nanjing Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Cohort A

Cohort B

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Pathological complete response (pCR) rate

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

Secondary Outcome Measures

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

To describe the safety of the various regimens toxicity is compared between the two arms.

Objective response rate (ORR)

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.

Disease-free Survival (DFS)

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.

Event Free Survival (EFS)

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.

Distant-disease- free survival (DDFS)

DDFS is defined as the time period from randomization to the first event.

Full Information

NCT ID

NCT04717531

First Posted

January 17, 2021

Last Updated

June 2, 2021

Sponsor

The First Affiliated Hospital with Nanjing Medical University

1. Study Identification

Unique Protocol Identification Number

NCT04717531

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2021

Overall Recruitment Status

Recruiting

Study Start Date

June 3, 2021 (Actual)

Primary Completion Date

June 1, 2023 (Anticipated)

Study Completion Date

May 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

The First Affiliated Hospital with Nanjing Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

neoadjuvant, pyrotinib, HER2-positive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cohort A

Arm Type

Experimental

Arm Description

Arm Title

Cohort B

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pyrotinib

Other Intervention Name(s)

Intervention Description

400mg, qd, po, day 1-21

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

Intervention Description

6 mg/kg, day 1

Intervention Type

Drug

Intervention Name(s)

Pertuzumab

Other Intervention Name(s)

Intervention Description

420 mg, day 1

Intervention Type

Drug

Intervention Name(s)

Docetaxel

Other Intervention Name(s)

Intervention Description

100 mg/m2, day 1

Intervention Type

Drug

Intervention Name(s)

Epirubicin

Other Intervention Name(s)

Intervention Description

90mg/m2, day 1

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Intervention Description

600 mg/m2, day 1

Primary Outcome Measure Information:

Title

Pathological complete response (pCR) rate

Description

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

Time Frame

up to 30 weeks

Secondary Outcome Measure Information:

Title

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

Description

To describe the safety of the various regimens toxicity is compared between the two arms.

Time Frame

up to 30 weeks

Title

Objective response rate (ORR)

Description

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.

Time Frame

up to 30 weeks

Title

Disease-free Survival (DFS)

Description

Time Frame

Following surgery, every 12 months until Year 10

Title

Event Free Survival (EFS)

Description

Time Frame

From date of randomization until follow-up to 10 years

Title

Distant-disease- free survival (DDFS)

Description

DDFS is defined as the time period from randomization to the first event.

Time Frame

From date of randomization until follow-up to 10 years

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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: 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. 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: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jue Wang, MD

Phone

00862568308172

wangjue200011@njmu.edu.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Xiaoming Zha, MD

Organizational Affiliation

The First Affiliated Hospital with Nanjing Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

the First Affiliated Hospital of Nanjing Medical University

City

Nanjing

State/Province

Jiangsu

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jue Wang, MD

Phone

00862568308172

wangjue200011@njmu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

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

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