Clinical trial NCT03728829: Targeted Next Generation Sequencing for the Efficacy of Trastuzumab Neoadjuvant Chemotherapy in Breast Cancer
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Observational
Prospective
Keywords: breast cancer
HER2 positive
next generation sequencing
trastuzumab
neoadjuvant chemotherapy
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
Collaborators: name: OrigiMed
First posted: 2018-11-02
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 100

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.

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

Primary outcomes:
measure: genetic profile sequenced by a pan-cancer gene panel
timeFrame: 1 year
Secondary outcomes:
measure: pCR
timeFrame: 1 year
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 1 year
Other outcomes:
Locations:
city: Shijiazhuang
country: China
facility: Fourth Hospital of Hebei Medical University, China
state: Hebei
Study officials:
affiliation: Hebei Medical University Fourth Hospital
name: Baoen Shan, MD,PhD
role: STUDY_CHAIR
References: