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Targeting the Hippo Transducer TAZ in Breast Cancer With Statins

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)

Status
UNKNOWN
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02416427
Acronym
TRINACRIA
Enrollment
78
Registered
2015-04-15
Start date
2015-05-31
Completion date
2016-12-31
Last updated
2015-04-15

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Neoplasms

Keywords

Atorvastatin, TAZ, Hippo pathway, ki67

Brief 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.

Interventions

DRUGAtorvastatin

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

Sponsors

Regina Elena Cancer Institute
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No

Inclusion criteria

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

Design outcomes

Primary

MeasureTime frame
Ki-67 reduction below the 15% (marker response).4 weeks

Secondary

MeasureTime frameDescription
• Decreased TAZ expression4 weeksReduced 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)
Pathway inhibition4 weeksDecreased 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).

Contacts

Primary ContactMarcello Maugeri Saccà, MD
maugeri@ifo.it+39065266

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026