Colorectal cancer and triple negative breast cancer patients (TNBC) who shown overexpression of fascin1 in the diagnostic biopsy tissue.
Conditions
Interventions
Trade Name: Imipramine
Product Name: Imipramine
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: IMIPRAMINE
CAS Number: 50-49-7
Pharmaceutical form of the placebo: Capsule, hard
Route of admini
Sponsors
Fundación para la formación e investigación sanitarias de la Región de Murcia
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients over 18 years. 2. Diagnosis by biopsy. 3. Overexpression of fascin1 in primary tumour (immunohistochemistry) as described in Conesa-Zamora et al. 2013. 4. Resectable tumour. 5. Ability to consent to treatment: patients or their legally authorized representative must be informed of the research nature of this study and must sign and give their informed consent in writing. 6. Candidate adjuvant colon cancer: stage II with poor prognostic factors and stage III or 7. Rectal cancer candidates for neo-adjuvant therapy or 8. Non-metastatic triple negative breast cancer candidates for neo-adjuvant therapy. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Metastatic disease at diagnosis or not candidates for neo-adjuvant therapy. 2. Colorectal cancer with clinical symptoms of sub-obstruction or obstruction. 3. Known diagnosis of major depressive disorder, bipolar depression, or psychosis. 4. ECOG 3 or 4 (see annexes). 5. Renal impairment defined as glomerular filtration rate 2 mg / dl. 7. fulfilment of the study requirements. 8. History of heart disease (arrhythmia, conduction abnormality, congenital long QT syndrome, or prolonged QTc rhythm seen during initial electrocardiogram> 480 ms). 9. Current use of selective serotonin or norepinephrine reuptake inhibitors (SSRIs, SNRIs), monoamine oxide inhibitors (MAOIs), tramadol or trazadone; or use of these drugs within 14 days prior to enrolment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the effect of the imipramine treatment on the development of histological manifestations associated with the mesenchymal epithelial transition during the period of time from the analysis of the diagnostic biopsy to the surgical resection intervention.;Secondary Objective: 1. Monitoring of minimal residual disease using circulating DNA: It will be analysed by liquid biopsy quantification and digital PCR of those mutations found in the primary tumour. 2. Serum Fascin1 expression quantification in plasma sample: It would be evaluated by ELISA assay.;Timepoint(s) of evaluation of this end point: Depending on type cancer: - Colon cancer: 2-6 weeks. - Rectal cancer: 15-23 weeks. - Triple negative breast cancer (TNBC): 20-24 weeks.;Primary end point(s): Comparison of the histological traits of invasive tumour front of the surgical tumour resection specimen between the intervention group and the placebo group: 1. Fascin1 expression in tumour tissue: It will be analysed by immunohistochemistry and the application of Immunoscore. 2. Histological manifestations of the epithelial-mesenchymal transition (EMT): Tumour budding, cytoplasmic pseudo-fragments, infiltrating growth pattern and poorly differentiated nests. It will be evaluated by histological analysis. 3. Invasive histological manifestations: discontinuous extramural extension, lymphatic, venous and perineural infiltration. It will be evaluated by histological analysis. 4. Histological manifestation of the immune response: Peritumoral and intratumour lymphocyte infiltration. It will be evaluated by histological analysis. 5. EMT molecular manifestations: FSCN1, SNAIL and SLUG gene expression. It will be evaluated by NGS analysis of the primary tumour. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Monitoring of minimal residual disease using circulating DNA: It will be analysed by liquid biopsy quantification and digital PCR of those mutations found in the primary tumour. 2. Serum Fascin1 expression quantification in plasma sample: It would be evaluated by ELISA assay.;Timepoint(s) of evaluation of this end point: Depending on type cancer: - Colon cancer: 2-6 weeks. - Rectal cancer: 15-23 weeks. - Triple negative breast cancer (TNBC): 20-24 weeks. | — |
Countries
Spain
Contacts
Public ContactMaria Muñoz
Plataforma EECC IMIB
Outcome results
None listed