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

Observational Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03728829
• Other study ID #: YLiu
• Status: Recruiting
• Start date: July 2021
• Est. completion date: December 31, 2022

Study information

• Verified date: July 2021
• Source: Hebei Medical University Fourth Hospital
• Contact: Yunjiang Liu, MD, PhD
• Phone: +86-311-8609-5588
• Email: lyj818326[@]126.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2022
• Est. primary completion date: October 30, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Observational
• Prospective

Intervention

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).

Locations

Country	Name	City	State
China	Fourth Hospital of Hebei Medical University, China	Shijiazhuang	Hebei

Sponsors (2)

Lead Sponsor	Collaborator
Hebei Medical University Fourth Hospital	OrigiMed

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	pCR	The pathological complete response (pCR) rate of patients treated with trastuzumab neoadjuvant chemotherapy.	1 year
Secondary	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