Neoadjuvant Study of Pyrotinib in Patients With HER2 Positive Breast Cancer

Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Docetaxel and Carboplatin in Patients With HER2 Positive Early Stage or Locally Advanced Breast Cancer: a Single-arm, Ahead, Open-label Study

This is a randomized, double-blind multicenter Phase III study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus docetaxel and Carboplatin versus placebo and trastuzumab plus docetaxel and Carboplatin given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Breast Diseases; Neoplasm, Breast
• Intervention / Treatment: Drug: Pyrotinib; Drug: Trastuzumab; Drug: Docetaxel; Drug: Carboplatin; Drug: Placebo Oral Tablet

Detailed Description

The investigators hypothesized that the experimental group (Pyrotinib+Trastuzumab+Docetaxel+ Carboplatin) could have a higher Pathological Complete Response (pCR) rate than the control group (Placebo +Trastuzumab+Docetaxel+ Carboplatin) in neoadjuvant chemotherapy.

It is proposed that 100 participants will be enrolled in this study. The target population is women with early breast cancer (stage of T1-4N0-3M0) who are eligible for primary systemic therapy.

The primary objective of the trial is to determine the pCR rate. The secondary objective of the trial is to determine the Event-free survival(EFS), Disease-free Survival (DFS), Distance Disease-free Survival (DDFS), Objective Response Rate (ORR) rate.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Zhejiang Cancer hospital
      • Contact: xiaowen ding, Dr.; Phone Number: +8613588054604; Email: dingxw@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. female patients, 18 years ≤ age ≤ 80 years；
2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1
3. Histologically confirmed invasive breast cancer（early stage or locally advanced）
4. HER2 positive (HER2+++ by IHC or FISH+)
5. Known hormone receptor status.
6. Cardiovascular: Baseline left ventricular ejection fraction (LVEF)≥55% measured by ECHO
7. Signed informed consent form (ICF)

Exclusion Criteria:

1. Metastatic disease (Stage IV) or inflammatory breast cancer
2. Previous 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. Clinically relevant cardiovascular disease: Known history of uncontrolled or symptomatic angina, clinically significant arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled hypertension ≥180/110);
4. Unable or unwilling to swallow tablets.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; Pyrotinib+Trastuzumab+Docetaxel +Carboplatin	Drug: Pyrotinib; Pyrotinib: 400mg orally daily; Drug: Trastuzumab; Trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 6 cycles; Drug: Docetaxel; Docetaxel: 75mg/m2 for a total of 6 cycles; Drug: Carboplatin; Carboplatin: AUC=5 for a total of 6 cycles
Placebo Comparator: Control group; Placebo Oral Tablet+Trastuzumab+Docetaxel +Carboplatin	Drug: Trastuzumab; Trastuzumab:8mg/kg iv load followed by 6mg/kg iv 3-weekly for a total of 6 cycles; Drug: Docetaxel; Docetaxel: 75mg/m2 for a total of 6 cycles; Drug: Carboplatin; Carboplatin: AUC=5 for a total of 6 cycles; Drug: Placebo Oral Tablet; Placebo Oral Tablet: 400mg orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery.	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	Disease-free Survival	Following surgery until Year 3
ORR	Objective Response Rate	Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months
DDFS	Distance Disease-free Survival	Following surgery until Year 3
EFS	Event-free survival	Following surgery until Year 3

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: November 21, 2018
• First Submitted That Met QC Criteria: November 27, 2018
• First Posted (Actual): November 28, 2018

Study Record Updates

• Last Update Posted (Actual): August 13, 2019
• Last Update Submitted That Met QC Criteria: August 8, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Neoplasms; Breast Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Carboplatin; Trastuzumab
• Other Study ID Numbers: TCHP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No