Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Pathologic Complete Response

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Afatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Drug: Afatinib (single group assignment)

1. First phase: Afatinib montherapy
2. The following phases: combination with oral afatinib and weekly paclitaxel in a 3-weekly course for total of four courses.

1. Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not
2. Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course.

PeiYing Liu

Sue-Huey H. Chen

Chiun-Sheng Huang

Chiun-Sheng Huang, PhD

\[Background\]: Triple-negative breast cancer (TNBC) is defined by a lack of expression of both estrogen and progesterone receptor as well as human epidermal growth factor receptor 2 (HER-2). TNBC is characterized by distinct molecular, histological and unfavorable clinical features despite the high rates of response to chemotherapy. Based on the above reasons, it is important to emergently develop novel therapies and/or treatment strategies to increase treatment efficacies and the survival rate of TNBC.

\[Rationale\]: Overexpression of epidermal growth factor receptor (EGFR/ErbB1) and EGFR mutation have been reported in TNBC and may therefore be a valid target for anti-tumor therapy in TNBC. Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in triple-negative breast cancer cell lines and xenograft models of breast cancer, and clinical activity in phase I studies. Based on the assumption that uncontrolled ErbB-signaling is directly related to an increased oncogenic potential in TNBC, the studying afatinib in the neoadjuvant treatment of TNBC patients is important and provides a novel therapy.

\[Aims\] The primary endpoint is to evaluate the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients receiving neoadjuvant treatment. The secondary endpoints are to evaluate the clinical response and safety of afatinib with and without paclitaxel, and to explore the different afatinib-affecting downstream molecular pathways as well as potential biomarkers predicting the response of afatinib with and without paclitaxel.

\[Patients and methods\]: Patients with TNBC (clinical T2-T3, N0-N1, M0; clinical T1-3, N1-2, M0; or any T4a tumor) and received neoadjuvant treatment will included in this open, label, multi-center phase II study. Our schema is as follows: (1) Afatinib 40 mg per day for 14 days, then evaluation, every subject will go into the following phase no matter whether she had response or not (2) the following phase (the combination with afatinib and paclitaxel): Afatinib 40 mg per day, day 1 to day 21, in combination with paclitaxel 80 mg/m² on days 1, 8, 15 in a 3-weekly course. In addition to the clinical assessment, we will evaluate the potential predictive biological markers of activity of Afatinib with and without paclitaxel and dynamic changes of molecular makers (\[serum and tissue samples: before treatment, 2 weeks after treatment, and operation timing\]; potential molecules, such as EGFR, EGFR-signaling, FGFR, FGFR-signaling, ERK, p53, NF-κB, and etc. were evaluated through the immunohistochemical stains, mutation analysis, mRNA \[RT-PCR\], single nucleotide polymorphism analysis, and FISH analysis). In addition, the genetic expression profiles will be compared between afatinib-responsive and afatinib-unresponsive samples.

\[Expected Results\]: The promising clinical activity, tolerable toxicity, and potential biomarkers of afatinib with and without paclitaxel in TNBC patients receiving neoadjuvant setting will be demonstrated. The results from this study can be used to conduct a larger trial that would allow us to confirm or validate the hypotheses generated.

Objects: Phase II study

Primary Objective :

To evaluate the efficacy of combination of afatinib and weekly paclitaxel as assessed by pathologicalresponse in the residual tumor.

Secondary Objectives:

1. Efficacy of afatinib as assessed by the ultrasound of the breast.
2. Adverse effect of afatinib monotherapy and the combination of afatinib and weekly paclitaxel.
3. Correlation between baseline potential biomarkers and radiological response of afatinib monotherapy.
4. Correlation between down- or up-regulation of potential biomarkers (in pre-treatment biopsy and surgical specimen) and radiological response to afatinib and paclitaxel.
5. To identify the pharmacodynamic biomarkers, the following translational researches will be carried out on initial tumor biopsy and surgical specimen.
6. To evaluate the dynamic changes of circulating tumor cells and cell-free DNA after afatinib monotherapy and after the combination of afatinib and weekly paclitaxel.

Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib

An Open Label, Phase II Trial of Afatinib With Paclitaxel for the Neoadjuvant Treatment of Triple-Negative Breast Cancer and Research of Biomarkers of Activity and Efficacy of Afatinib

Evaluation of the pathologic complete response of the combination of afatinib and weekly paclitaxel in TNBC patients with neoadjuvant treatment.

The radiologic response will be assessed on ultrasound of the breast.

circulating tumor cells is a new technigue compatible with cell search.

National Taiwan University Hospital

Patients with triple-negative or HER2 Positive breast cancer, axillary lymph node metastasis who underwent NAC are eligible for this study. Axillary lymph node metastasis is confirmed by fine needle aspiration (FNA) or core needle biopsy (CNB) at initial diagnosis. CT-based radiomics will be uesd in evaluating the response and predicting pCR of metastatic lymph nodes after NAC in breast cancer patients.

Lize Wang, MD

Yingjian He, MD

Jiwei Wang, MD

This is a prospective, single-center, non-randomized, non-controlled observational study.

Almost 55-62% of patients with triple-negative or human epidermal growth factor receptor 2 (HER2) positive, node-positive breast cancer achieve an axillary pathologic complete remission (pCR) after neoadjuvant chemotherapy (NAC). To avoid surgery post-NAC, it is paramount to accurately identify patients who achieve pCR in axillary lymph node (ALN). We found that patients with normal-appearing lymph nodes on computed tomography (CT) based radiomics of the axilla after chemotherapy had a lower risk of developing residual nodal disease. However, the features of CT-based radiomics for pCR ALN following NAC has not been established yet. This study aimed to assess the performance of CT-based radiomics in evaluating the response and predicting pCR of metastatic lymph nodes after NAC in breast cancer patients.

Axillary lymph node status are determined in FNA/CNB and surgical specimen.

CT-based Radiomics of ALN pCR (ypN0) in Breast Cancer Undergoing NAC

Computed Tomography-based Radiomics of Axillary Lymph Node Pathological Complete Remission (ypN0) in Breast Cancer Undergoing Neoadjuvant Chemotherapy

Sensitivity, specificity, positive-predictive value (PPV) and negative-predictive value (NPV) of CT-based radiomics for axillary lymph node status after neoadjuvant chemotherapy will be assessed.

The diagnostic performance of CT-based radiomics for the evaluation of ALN after NAC was evaluated with receiver operating characteristic (ROC) curve analysis. The diagnostic accuracy was estimated by calculating the area under the ROC curve

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib	NCT02511847	Triple Negative...	Afatinib	20 Years -	National Taiwan University Hospital
CT-based Radiomics of ALN pCR (ypN0) in Breast Cancer Undergoing NAC	NCT04457700	Triple-negative... HER2-positive B...		18 Years - 70 Years	Peking University
Trial of Afatinib With Paclitaxel for Neoadjuvant Therapy of TNBC and Research of Biomarkers of Afatinib	NCT02511847	Triple Negative...	Afatinib	20 Years -	National Taiwan University Hospital

Spots Global Cancer Trial Database for pathologic complete remission