Targeted Next Generation Sequencing for the Efficacy of Trastuzumab Neoadjuvant Chemotherapy in Breast Cancer

• Conditions: Observational; Prospective
• Interventions: Drug: Trastuzumab+TP

• Registration Number: NCT03728829
• Lead Sponsor: Hebei Medical University Fourth Hospital

Brief Summary

To explore the genetic background of patients with HER2 positive breast cancer that benefit from trastuzumab combined with neoadjuvant chemotherapy, identify clinically actionable mutations that associated with trastuzumab resistance or drug efficacy, we designed this Observational phase II trial. The primary endpoint is genetic profile of HER2+ breast cancer patients treated with trastuzumab combined neoadjuvant chemotherapy. Secondary endpoints included pathological complete response (pCR) rate and safety.

Detailed Description

Currently, patients with stage II-III breast cancer still accounts for a large population in China, and neoadjuvant therapy is considered the standard treatment for them. The pathological complete response (pCR) rate takes for an indicator for regimens efficacy, and the achievement of pCR after neoadjuvant chemotherapy is associated with favorable outcomes including disease-free survival and overall survival.

HER2+ breast cancer represents an invasive and poor prognosis subtype, and the efficacy of neoadjuvant therapy for these patients has been greatly augmented by the addition of trastuzumab. However, more than 50% of HER2+ breast cancer patients treated with trastuzumab combined neoadjuvant chemotherapy cannot achieve pCR, even experience primary drug resistance and rapid disease progression. Therefore, to explore the genomic features of the population that benefited from trastuzumab combined with chemotherapy is of great significance for personalized treatment of HER2+ breast cancer, aiming to avoid overtreatment and identify clinically actionable mutations for future therapy instructions.

Study Timeline

• Study First Submitted: 2018-10-26
• Study First Submitted QC: 2018-10-31
• Study First Posted: 2018-11-02
• Status Verified: 2021-07
• Study Start: 2021-07
• Last Update Submitted: 2021-07-06
• Last Update Posted: 2021-07-09
• Primary Completion: 2022-10-30
• Study Completion: 2022-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 100

Inclusion Criteria

• women aged 18-70 years old at the time of diagnosis of primary breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
• Stage III breast cancer according to the 7th Edition of Cancer staging Manual of American Joint Committee on Cancer (AJCC)
• full assessment of ER, PR and HER2 status of primary tumor in accordance with the American Society of Clinical Oncology (ASCO) guidelines
• pathological diagnosis and all courses of treatment confirmed

Exclusion Criteria

• any known metastatic disease, by physical exam or by imaging studies such as computed tomography (CT)/magnetic resonance imaging (MRI), at the time of study entry
• any previous exposure to chemotherapy, radiotherapy, or endocrine therapy
• left ventricular ejection fraction (LVEF) < 55% by Echocardiogram (ECHO) or multigated acquisition scan (MUGA) or significant clinical symptoms or signs of heart failure
• major organ dysfunction, inclusive of bone marrow, renal, liver and hepatic function, that would prohibit patients from receiving standard chemotherapy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Trastuzumab+TP neoadjuvant chemotherapy	Trastuzumab+TP	100 cases of patients with stage II-III HER2+ breast cancer will be assigned participants to neoadjuvant treatment regimen, including Trastuzumab combined with Docetaxel and Carboplatin. 5-10 ml peripheral blood will be collected from each patient and formalin fixed paraffin embedded (FFPE) blocks/sections or fresh tumor tissues/biopsies will be obtained from the hospitals before and after neoadjuvant therapy. The genomic characteristics between patients achieved pCR and non-pCR will be analyzed. The clinically actionable mutations for future therapy instructions will be identified.

Primary Outcome Measures

Name	Time	Method
genetic profile sequenced by a pan-cancer gene panel	1 year	analyze the genetic profile of HER2+ breast cancer patients treated with trastuzumab combined neoadjuvant chemotherapy by targeted next generation sequencing on a pan-cancer gene panel

Secondary Outcome Measures

Name	Time	Method
pCR	1 year	The pathological complete response (pCR) rate of patients treated with trastuzumab neoadjuvant chemotherapy.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	1 year	The incidence of adverse events of patients treated with trastuzumab neoadjuvant chemotherapy, including Cardiac toxicity, leukopenia, etc.

Trial Locations

Locations (1)

Fourth Hospital of Hebei Medical University, China; 🇨🇳 Shijiazhuang, Hebei, China