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

NCT ID: NCT03728829

Last Updated: 2021-07-09

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-07-31
• Study Completion Date: 2022-12-31

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.

Conditions

Observational; Prospective

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Trastuzumab+TP neoadjuvant chemotherapy

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.

Trastuzumab+TP

Intervention Type: DRUG

Trastuzumab (4 mg/kg loading dose, then 2 mg/kg I.V., every week, totally 17 weeks (6 cycles)) combined with TC neoadjuvant chemotherapy (Docetaxel 75 mg/m2 I.V., day 1, Carboplatin 400 mg/kg, I.V., day 2, every 3 weeks, totally 6 cycles).

Interventions

Trastuzumab+TP

Trastuzumab (4 mg/kg loading dose, then 2 mg/kg I.V., every week, totally 17 weeks (6 cycles)) combined with TC neoadjuvant chemotherapy (Docetaxel 75 mg/m2 I.V., day 1, Carboplatin 400 mg/kg, I.V., day 2, every 3 weeks, totally 6 cycles).

Intervention Type: DRUG

Other Intervention Names

Trastuzumab+Docetaxel+Carboplatin

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

OrigiMed

INDUSTRY

Sponsor Role: collaborator

Hebei Medical University Fourth Hospital

OTHER

Sponsor Role: lead

Responsible Party

Liu Yunjiang

Vice President, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Baoen Shan, MD,PhD

Role: STUDY_CHAIR

Hebei Medical University Fourth Hospital

Locations

Fourth Hospital of Hebei Medical University, China

Shijiazhuang, Hebei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yunjiang Liu, MD, PhD

Role: CONTACT

lyj818326@126.com

+86-311-8609-5588

Facility Contacts

Yunjiang Liu, M.D., Ph.D.

Role: primary

lyj818326@126.com

+86-311-86095588

Other Identifiers

YLiu

Identifier Type: -

Identifier Source: org_study_id