Newly diagnosed, untreated, operable triple negative breast cancer MedDRA version: 18.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: ZOMETA - 4 MG POLVERE E SOLVENTE PER SOLUZIONE PER INFUSIONE ENDOVENOSA 1 FLACONCINO + 1 FIALA SOLVENTE 5 ML
Pharmaceutical Form: Powder and solvent for solution for infusion
Sponsors
IRCCS- ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients with newly diagnosed, untreated, operable triple negative breast cancer (TNBC), intended to definitive breast surgery and suitable for pre-operative therapy with zol. Patients must meet all the following criteria for study entry: - Histologically confirmed diagnosis of non-metastatic operable TNBC subjected to diagnostic core biopsy - TNBC defined as HER2/ER/PgR negative receptors - Age = 18 years old - ECOG (Eastern Cooperative Oncology Group) performance status = 1 - Ki67 and p53 expression determined by IHC - Availability of paraffin-embedded tumor block (FFPE) taken at diagnostic biopsy for IHC and RT-PCR molecular determinations - Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to start of trial. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months (female patients) and 6 months (male patients) after discontinuation of treatment. - Written informed consent signed prior to enrolment according to ICH/GCP. 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 22 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: - Presence of metastatic disease - Clinical indication of debulking neo-adjuvant treatment - Previous investigational treatment for any condition within four weeks prior to study registration -Treatment with bisphosphonates, denosumab or other drug that, in the Investigator’s judgment, affects bone metabolism -Treatment with statins or other drugs that, in the Investigator’s judgment, potentially affect the mevalonate pathway - Any previous treatment for the currently diagnosed breast cancer, including radiation therapy, chemotherapy, biotherapy and/or hormonal therapy - Inadequate bone marrow, hepatic or renal function including the following: • Hb 1.5 x ULN, excluding cases where elevated bilirubin can be attributed to Gilberts Syndrome • AST (SGOT), ALT (SGPT) > 2.5 x ULN • Creatinine > 1.2 x ULN, calcium < 8.6 mg/dL - Co-existing active infection or concurrent illness that, at the judgment of the investigator, contra-indicate the inclusion of the patient in the study - Co-existing dental diseases that form a contraindication to the use of zol - Any medical or other condition that in the Investigator’s opinion renders the patient unsuitable for this study due to unacceptable risk - Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study assessment and procedures - Known hypersensitivity to any excipients of zoledronate - Anticipation of need for major surgical procedure during the course of the trial - Pregnant or breast feeding women.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The study is primarily aimed at assessing the anti-tumor activity of pre-operative zoledronate measured through its effect on the Ki67 proliferative surrogate biomarker, in patients with triple negative breast cancer selected according to the p53 expression (high vs low p53 expression).;Secondary Objective: To investigate the effect of zoledronate on critical genes/proteins related to p53 and mevalonate pathways, p53/PIN1 and YAP/TAZ, analyzed at the time of diagnosis (core biopsy) and at definitive surgery (breast cancer resection). To study the safety profile of zoledronate, evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale, version 4.0 and by the occurrence of serious adverse reactions.;Primary end point(s): The study is primarily aimed at assessing the anti-tumor activity of pre-operative zoledronate (zol), measured through its effect on the Ki67 proliferative surrogate biomarker, in patients with TNBC selected according to the p53 expression (high vs low p53 expression). Primary endpoint of the study is the proportion of responder patients, defined as those with at least 30% reduction in Ki67 at surgery with respect to core-biopsy analysis. Prior to enrolment, the FFPE diagnostic core biopsy specimens will be analyzed by the study pathologist to determine the presence of invasive TNBC and the Ki67/p53 values. The ki67/p53 evaluation will be then repeated after treatment at the time of definitive surgery.;Timepoint(s) of evaluation of this end point: The primary endpoint (proportion of responder patients, defined as those with at least 30% reduction in Ki67 at surgery with respect to core-biopsy analysis) will be evaluated after the definitive breast surgery planned seven days after study treatment (i.e. Zometa administration). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To investigate the effect of zoledronate on critical genes/proteins related to p53 and mevalonate pathways, p53/PIN1 and YAP/TAZ, analyzed at the time of diagnosis (core biopsy) and at definitive surgery (breast cancer resection). After enrolment, the FFPE core biopsy will be tested for critical genes/proteins expression (by RT-PCR and IHC), including p53/PIN1 and YAP/TAZ. The same evaluations will be performed after treatment, at the time of definitive surgery. To study the safety profile of zoledronic acid, evaluated by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) scale, version 4.0 and by the occurrence of serious adverse reactions. ;Timepoint(s) of evaluation of this end point: The evaluation of critical genes/proteins expression (by RT-PCR and IHC), including p53/PIN1 and YAP/TAZ will be performed on the core biopsy and after treatment, at the time of definitive surgery, planned seven days after study treatment. Zometa safety profile will be evaluated through the duration of the study and post treatment at 30 and 60 days following definitive surgery. | — |
Countries
Italy
Contacts
Public ContactLaboratorio Ricerca Clinica
IRCCS-Istituto di Ricerche Farmacologiche Mario Negri
Outcome results
None listed