The Role of Bexarotene in Inducing Susceptibility to Chemotherapy in Metastatic TNBC

Study Overview
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Brief Summary
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Triple-negative breast cancer (TNBC) is biologically aggressive and has limited systemic treatment options, often compounded by treatment resistance. Cell state transitions, e.g. epithelial-to-mesenchymal transition (EMT) govern cancer cell behaviour. The investigators hypothesize that by inducing change in cell state change, TNBC cells that have manifested taxane-resistance will be more sensitized to subsequent chemotherapy.

Official Title
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Metastatic Triple-Negative Taxane-Resistant Breast Cancer: Investigating the Role of Bexarotene in Inducing Susceptibility to Chemotherapy by Differentiating Cancer Cells From a Mesenchymal-Like to an Epithelial-Like Phenotype

Conditions
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Metastatic Triple-Negative Breast Carcinoma

Intervention / Treatment
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* Drug: Bexarotene
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically proven metastatic TNBC Patients whose TNBC has progressed after prior taxane therapy in the (neo)adjuvant or metastatic setting, and have not received Capecitabine or 5-fluorouracil Females aged 21 years and older ECOG performance status 0 or 1 Life expectancy greater than three months Patients have normal organ and marrow function Site(s) of disease amenable to serial bedside biopsies before, during and after study treatment Exclusion Criteria: Previous palliative radiotherapy to potentially biopsy-able lesion Active symptomatic central nervous system (CNS) metastases Spinal cord compression not definitively treated with surgery and/or radiation Uncontrolled pleural effusion, pericardial effusion, ascites requiring recurrent drainage procedures

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bexarotene and Capecitabine<br> | Drug: Bexarotene<br>* Administered orally once a day. Starting dosage: 200mg/m^2<br>* Other names: Targretin;Drug: Capecitabine<br>* Administered orally twice a day. Dosage: 1000mg/m^2<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumour transcriptome by RNA sequencing | To characterize the changes in tumour transcriptome upon treatment | From time of first biopsy before the start of treatment, to disease progression, up to 2 years | 
| Tumour protein profile by multiplex immunohistochemistry | To characterize the changes in tumour protein profile upon treatment | From time of first biopsy before the start of study treatment, to disease progression, up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidences of treatment related adverse events |  | From time of start of study treatment, to 28 days after last dose of study treatment, up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bexarotene