Targeting the Hippo Transducer TAZ in Breast Cancer With Statins

Breast Neoplasms Clinical Trial

— TRINACRIA  

Official title:

A Phase II, Randomized, Non-comparative, Pre-surgical Study of Atorvastatin or Observation in Ki-67 Positive, TAZ-expressing Early Breast Cancer Patients (TRINACRIA Trial)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02416427
• Other study ID #: 637/15
• Status: Not yet recruiting
• Phase: Phase 2
• First received: April 2, 2015
• Last updated: April 9, 2015
• Start date: May 2015
• Est. completion date: December 2016

Study information

• Verified date: April 2015
• Source: Regina Elena Cancer Institute
• Contact: Marcello Maugeri Saccà, MD
• Phone: +39065266
• Email: maugeri[@]ifo.it
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial Summary

This pre-surgical, window-of-opportunity study is designed to investigate whether atorvastatin reduces the proliferation marker Ki-67 via modulation of the Hippo transducer TAZ.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 78
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion:

• Signed written informed consent

• Female aged >18 years and <75 years at the time of the enrolment

• Histologically confirmed Breast Cancer (BC) independently on the intrinsic subtype

• Stage I-IIa BC patients candidate for elective surgery

• BC expressing Ki-67 = 15% and TAZ > 10% in diagnostic core biopsies

• Adequate baseline organ function

• Negative pregnancy test

Exclusion:

• Previous systemic therapy including chemotherapy, hormone therapy and targeted agents

• Administration of an investigational drug prior to enrolment

• History of another malignancy, except for a history of completely resected non-melanoma skin cancer or successfully treated cervical in situ carcinoma

• Eastern Cooperative Oncology Group (ECOG) performance status =2

• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome and asymptomatic gallstones)

• Serious cardiac illness or medical conditions including but not confined to: history of documented congestive heart failure (CHF) or systolic dysfunction (LVEF <50%); high-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV-block, supraventricular arrhythmias which are not adequately controlled); angina pectoris requiring antianginal medication; clinically significant valvular heart disease; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic >100mm Hg)

• Have a concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent)

• Current or recent therapy with statins for hypercholesterolemia or other lipid-lowering drugs

• Current or recent therapy with glucose-lowering drugs for diabetes

• Current or recent therapy with strong CYP3A4 inhibitors (e.g., clarithromycin, HIV protease inhibitors, itraconazole) given potential interactions with atorvastatin

• Current or recent therapy with gemfibrozil or other fibrates given potential interactions with atorvastatin.

• Patients who are pregnant or breastfeeding

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Atorvastatin
Atorvastatin will be administered at 80 mg/day for 3 weeks in the time window between diagnostic biopsy and curative surgery

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regina Elena Cancer Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ki-67 reduction below the 15% (marker response).		4 weeks	No
Secondary	• Decreased TAZ expression	Reduced TAZ expression evaluated by IHC when comparing pre- and post-treatment samples. Staining intensity will be graded on a four-grade scale (0: negative, 1: weak, 2: moderate, 3: strong). The final score will be obtained by considering staining intensity, percentage of expressing cells, and localization (nuclear versus cytoplasmic)	4 weeks	No
Secondary	Pathway inhibition	Decreased expression of TAZ targets (AXL and CTGF) and Atorvastatin target (HMGCoAR) evaluated by IHC when comparing pre- and post-treatment samples. Staining intensity for all the molecular endpoints analyzed will be graded on a four-grade scale (0: negative, 1: weak, 2: moderate, 3: strong).	4 weeks	No