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

An Observational Phase II Trial of Targeted Next Generation Sequencing Analysis for the Efficacy of Trastuzumab Neoadjuvant Chemotherapy in Patients With HER2 Positive Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Prospective; Observational
• Intervention / Treatment: Drug: Trastuzumab+TP

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 Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Yunjiang Liu, MD, PhD; Phone Number: +86-311-8609-5588; Email: lyj818326@126.com

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • Fourth Hospital of Hebei Medical University, China
      • Contact: Yunjiang Liu, M.D., Ph.D.; Phone Number: +86-311-86095588; Email: lyj818326@126.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

• Sampling Method: Probability Sample

Study Population

100

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

Drug: 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).; Other Names: Trastuzumab+Docetaxel+Carboplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
genetic profile sequenced by a pan-cancer gene panel	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	1 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Hebei Medical University Fourth Hospital
• Collaborators: OrigiMed
• Investigators: Study Chair: Baoen Shan, MD,PhD, Hebei Medical University Fourth Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2021
• Primary Completion (Anticipated): October 30, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: breast cancer; neoadjuvant chemotherapy; trastuzumab; HER2 positive; next generation sequencing
• 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, Immunological; Docetaxel; Carboplatin; Trastuzumab
• Other Study ID Numbers: YLiu

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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