Neoadjuvant Study of Pyrotinib and Trastuzumab Plus Vinorelbine in Trastuzumab-refractory HER2-Positive Breast Cancer.

Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Vinorelbine in Trastuzumab-refractory HER2-Positive Early Stage or Locally Advanced Breast Cancer Patients.

This study is a single-arm, prospective, open label clinical study for evaluating the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus Vinorelbine given as neoadjuvant treatment in Trastuzumab-refractory HER2 positive early stage or locally advanced breast cancer.

Study Overview

• Status: Unknown
• Conditions: HER2 Positive Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib and Trastuzumab plus Vinorelbine

Detailed Description

Neoadjuvant therapy is the standard treatment for locally advanced breast cancer and is used to reduce tumors to make them operable, and to increase breast-conserving rates. In recent years, the anti-HER2 treatment mode, which is double-blocked by a combination of dual-targeted drugs, has obtained clinical approval in adjuvant therapy and neoadjuvant therapy. Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. Based on previous clinical studies, we designed the study to explore the possibility of Pyrotinib in combination with Trastuzumab plus Vinorelbine given as neoadjuvant treatment in HER2 positive early stage or locally advanced breast cancer.

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: xiuchun Chen; Phone Number: 18603719919; Email: cxc701024@163.com
• Study Contact Backup: Name: jianghua Qiao; Phone Number: 13592581572; Email: qiaojianghua1997@163.com

Participation Criteria

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, 18 years ≤ age ≤ 75 years. 2. Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-1. 3. Histologically confirmed invasive breast cancer:early stage or locally advanced,Primary tumour greater than 2 cm diameter 4. HER2 positive (HER2+++ by IHC or FISH+) 5. Subjects received neoadjuvant therapy with trastuzumab 2 weeks post-imaging evaluation Patients with a price of PD or SD. 6. Known hormone receptor status. 7. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L;Platelet count: ≥ 100 x 10^9/L;Hemoglobin: ≥ 9.0 g/dL;Total bilirubin: ≤ 1.5 x upper limit of normal (ULN);ALT and AST: ≤ 1.5 x ULN (or ≤ 5×ULN in patients with liver metastases);BUN and creatine clearance rate: ≥ 50 mL/min;LVEF: ≥ 50%;QTcF: < 470 ms for female and < 450 ms for male. 8. Signed the informed consent form prior to patient entry.

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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib + trastuzumab +Vinorelbine; Pyrotinib in Combination With Trastuzumab Plus Vinorelbine	Drug: Pyrotinib and Trastuzumab plus Vinorelbine; Pyrotinib:400mg orally daily Trastuzumab:8mg/kg ivgtt load followed by 6mg/kg ivgtt 3-weekly for a total of 4 cycles Vinorelbine :25mg/m2 ivgtt 3-weekly for a total of 4 cycles,d1 d8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	[Time Frame: Baseline up to cycle 4 (assessed at Baseline, at the time of pre-surgery)up to approximately 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR)	Percentage of Participants With Pathological Complete Response (pCR) at the Time of Surgery evaluated	Time Frame: through study completion, an average of 1 year
EFS	Event-free survival	Time Frame: Following surgery until Year 5
DFS	Disease-free Survival	Time Frame: Following surgery until Year 5
DDFS	Distance Disease-free Survival	Time Frame: Following surgery until Year 5

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: xiuchun Chen, Study Principal Investigator Henan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2019
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): December 30, 2020

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Trastuzumab-refractory
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Trastuzumab; Vinorelbine
• Other Study ID Numbers: HR-NeoBC-HN003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No