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Targeting the Hippo Transducer TAZ in Breast Cancer With Statins (TRINACRIA)

Primary Purpose

Breast Neoplasms

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Atorvastatin

About this trial

This is an interventional treatment trial for Breast Neoplasms focused on measuring Atorvastatin, TAZ, Hippo pathway, ki67

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Arm A

Arm B

Arm Description

Atorvastatin 80 mg/day for 3 weeks

Observation

Outcomes

Primary Outcome Measures

Ki-67 reduction below the 15% (marker response).

Secondary Outcome Measures

• 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)

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).

Full Information

NCT ID

NCT02416427

First Posted

April 2, 2015

Last Updated

April 9, 2015

Sponsor

Regina Elena Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT02416427

Brief Title

Targeting the Hippo Transducer TAZ in Breast Cancer With Statins

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2015

Overall Recruitment Status

Unknown status

Study Start Date

May 2015 (undefined)

Primary Completion Date

December 2016 (Anticipated)

Study Completion Date

December 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Regina Elena Cancer Institute

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Neoplasms

Keywords

Atorvastatin, TAZ, Hippo pathway, ki67

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Description

Atorvastatin 80 mg/day for 3 weeks

Arm Title

Arm B

Arm Type

No Intervention

Arm Description

Observation

Intervention Type

Drug

Intervention Name(s)

Atorvastatin

Intervention Description

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

Primary Outcome Measure Information:

Title

Ki-67 reduction below the 15% (marker response).

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

• Decreased TAZ expression

Description

Time Frame

4 weeks

Title

Pathway inhibition

Description

Time Frame

4 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Marcello Maugeri Saccà, MD

Phone

+39065266

Ext

2724

maugeri@ifo.it

12. IPD Sharing Statement

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Targeting the Hippo Transducer TAZ in Breast Cancer With Statins

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