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Pre-operative Zoledronate in Triple Negative Breast Cancer

NCT02347163 · Status: TERMINATED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 22

Last updated 2018-11-06

No results posted yet for this study

Summary

Recent evidences suggest that zoledronate (zol), one of the most used bisphosphonates (BPs) in the clinical setting for the prevention and treatment of bone metastasis in cancer patients, may have antitumor activity in early breast cancer in terms of improved disease free survival, overall survival and better response in BPs treated patients. BPs are mevalonate pathway inhibitors and one of the most intriguing hypothesis supporting their anticancer activity relies on the modulation of the mevalonate downstream metabolism. Biologically active mevalonate metabolites are involved in tumour cell proliferation and invasion and selected cancer subtypes may present a more pronounced mevalonate activity, able of maintaining an aggressive phenotype. The mevalonate pathway has deep impact on the function of YAP/TAZ, transcriptional regulators of tumour growth, and preclinical evidences suggest that BPs are able to interfere with YAP/TAZ expression, via mevalonate pathway. This study addresses the clinical role of BPs in triple negative breast cancer (TNBC) patients selected by the level of mevalonate pathway regulation, namely the p53 expression. This study is a multicenter single-arm, phase II study primarily aimed at assessing the anti-tumor activity of pre-operative zol measured through its effect on the Ki67 proliferative biomarker, in TNBC patients classified according to the p53 expression (high vs low p53 expression). Patients with newly diagnosed, untreated, operable TNBC, intended to definitive breast surgery and suitable for pre-operative therapy with zoledronate will receive a pre-operative, single administration of zol (4mg i.v.), 7 days before definitive breast surgery. Ki67 levels will be assessed in tumor samples collected at the time of diagnosis and after zoledronate treatment at the time of definitive surgery. The secondary objective of the study is to investigate the effect of zoledronate on critical genes/proteins related to p53 and mevalonate pathways, p53/PIN1 and YAP/TAZ, analyzed in the tumor tissue collected at the time of diagnosis and at definitive surgery. Zol safety profile will be evaluated by the NCI-CTCAE scale, version 4.0, and by the occurrence of serious adverse reactions. The total number of patients required is forty. The overall duration of the project is 32 months (30 months for accrual, followed by 2 months of follow-up after the recruitment of the last patient).

Conditions

Interventions

DRUG

Zoledronate

Patients fulfilling the eligibility criteria will be registered using a centralized system and will receive a pre-operative, single administration of zol (4mg i.v.), 7 days before definitive breast surgery .

Sponsors & Collaborators

  • Associazione Italiana per la Ricerca sul Cancro

    collaborator OTHER

  • Mario Negri Institute for Pharmacological Research

    lead OTHER

Principal Investigators

  • Alberto Zambelli, MD · Azienda Ospedaliera Papa Giovanni XXIII, Bergamo

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2015-02-03
Primary Completion
2018-06-08
Completion
2018-06-08

Countries

  • Italy

Study Locations

More Related Trials

Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02347163 on ClinicalTrials.gov