We investigated, in a population of patients with breast cancer, the combined effect of azithrocyn, docyciclin and vitamin C on biomarkers associated with cell proliferation MedDRA version: 21.0 Level: LLT Classification code 10079328 Term: Breast tumor excision System Organ Class: 100000004865
Conditions
Interventions
Product Name: Azitromicina
Product Code: [x]
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: AZITROMICINA
Current Sponsor code: NA
Other descriptive name: Azitromycin
Concentration unit:
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (1) accession through informed consent; (2) WHO Performance Status 0-1; (3) ability to swallow; (4) adult females; (5) Clinical stage 1-3 AJCC; (6) planned surgical intervention in accordance with the timing of the trial; (7) normal kidney and liver function; (8) diagnosis of invasive carcinoma verified by biopsy. 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) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: (1) previous treatments for breast cancer or other malignancies (except malignant skin tumors other than melanoma); (2) surgical treatments or antibiotics in the 4 weeks prior to entering the trial; (3) known intolerance or allergy to the drugs being tested; (4) presence of severe or uncontrolled systemic diseases; (5) concomitant neoadjuvant therapy; (6) surgery scheduled less than two weeks after the signing of the informed consent; (7) pregnancy or breastfeeding; (8) concomitant therapies with drugs capable of interacting with Doxycycline, Azithromycin or Vitamin C; (9) inability to understand and to wish; (10) homeless patients; (11) history of abuse or dependence on alcohol and / or drugs; (12) deficiency of the enzyme glucose 6P dehydrogenase.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to assess whether the DAV combination treatment reduces the proliferative activity of ther tumor, measured with an immunohistochemical method using anti-ki67 antibody;Secondary Objective: (1) to evaluate the effect of the DAV combination treatment with respect to changes in stem cell markers (ALDH, CD44 / 24), differentiation (nuclear and histological grade), mitochondrial mass (TOMM20), senescence (beta -galactosidase, lipofuscin), of apoptosis (Cleaved caspase 3, TUNEL assay), of angiogenesis (CD31), of regulation of the cell cycle (p27), measured with immunistochemical method, comparing the values on the tumor tissue obtained with preoperative biopsy and subsequently on whole tumor surgically removed; (2) to evaluate the molecular basis of possible resistance to antibiotic treatment; (3) identify and monitor the presence of circulating tumor cells (CTC); (4) assessing the effect of treatment on disease-free interval; (5) assessing whether the DAV combination treatment is more effective than the Doxycycline alone therapy (6) assessing the safety and tolerability of the DAV regime.;Primary end point(s): Reduction in Ki67 expression in post-treatment tumor samples compared to pre-treatment tumor core biopsies (from the same patient). Post-treatment samples will also be compared with untreated samples;Timepoint(s) of evaluation of this end point: End points will be evaluated at the diagnosis (bioptic material, pretreatment evaluation) and in the surgically-removed tumour tissue (post-treatment evaluation). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In post-treatment compared to pre-treatment patient tumor samples, as well as in post-treatment compared to untreated patient tumor samples: • Reduction in cancer stem cell markers (ALDH, CD44/24) • Increase in tumor differentiation markers (Nuclear grading and histological grading) • Reduction in mitochondrial markers (such as TOMM20) • Reduction in angiogenesis markers (CD31) • Reduction in senescence markers (beta-galactosidase and lipofuscin) • Increase in apoptotic markers (p27, cleaved caspase 3 and TUNEL) In post-treatment compared to pre-treatment patient blood samples: • Decreased levels of circulating tumor cells In post-treatment compared to pre-treatment patients: • Tumor mass is decreased In post-treatment compared to untreated patient tumor samples: • Alterations in genetic profiling • Alterations in proteomics profiling In post-treatment compared to untreated patients: • Elevated blood levels and tumor tissue levels of DAV (doxycycline, azithromycin and vitamin C) • Blood levels of CA15.3 are <30 U/ml at follow up every 4 months for the first 3 years and then every 6 months for the following two years • Radiological follow up (yearly mammography and ultrasound) show no signs of recurrence for 5 years In tumor samples from post-treatment patients compared to treated patients from the ABC trial using z-test for two proportions. • The reduction in cancer stem cells markers is enhanced as compared to data collected with the ABC trial;Timepoint(s) of evaluation of this end point: End points will be evaluated at the diagnosis (bioptic material, pretreatment evaluation) and in the surgically-removed tumour tissue (post-treatment evaluation). | — |
Countries
Italy
Contacts
Public ContactS.D. Anatomia Patologica I Universi
AOU Pisana
Outcome results
None listed