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
Overview
- Phase
- Phase 1
- Intervention
- Bexarotene
- Conditions
- Metastatic Triple-Negative Breast Carcinoma
- Sponsor
- National Cancer Centre, Singapore
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Tumour protein profile by multiplex immunohistochemistry
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
Bexarotene and Capecitabine
Intervention: Bexarotene
Bexarotene and Capecitabine
Intervention: Capecitabine
Outcomes
Primary Outcomes
Tumour protein profile by multiplex immunohistochemistry
Time Frame: From time of first biopsy before the start of study treatment, to disease progression, up to 2 years
To characterize the changes in tumour protein profile upon treatment
Tumour transcriptome by RNA sequencing
Time Frame: From time of first biopsy before the start of treatment, to disease progression, up to 2 years
To characterize the changes in tumour transcriptome upon treatment
Secondary Outcomes
- 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)