MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer

NCT ID: NCT03767335

Last Updated: 2025-06-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-13

Study Completion Date

2024-02-23

Brief Summary

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The main purpose of this open-label, dose-escalation, phase Ib study is to identify the appropriate dose of MEN1611 to be used in combination with Trastuzumab with/without Fulvestrant for the treatment of advanced or metastatic HER2-positive breast cancer

Detailed Description

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This Phase Ib study will investigate the safety and anti-tumor activity of daily oral doses MEN1611 in combination with Trastuzumab with/without Fulvestrant in female and male patients affected by advanced or metastatic HER2-positive breast cancer. Fulvestrant will be added to the post-menopausal patients with hormone-sensitive disease.

MEN1611 is an investigational drug which blocks a protein called PI3K (phosphoinositide 3-kinase) involved in cancer cells growth. The Maximum Tolerated Dose (MTD) of MEN1611 given as single agent was assessed in a phase I trial in patients with advanced solid tumors.

This Phase IB will start with a dose escalation part (Step 1) to identify the MTD of MEN1611 given in combination with Trastuzumab with/without Fulvestrant.

The study will continue with a cohort expansion (Step 2) to investigate the anti-tumor activity of the selected MEN1611 dose level considered to be tolerable by a Safety Review Committee.

Conditions

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Advanced or Metastatic Breast Cancer

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MEN1611

MEN1611 + Trastuzumab +/- Fulvestrant

Group Type EXPERIMENTAL

MEN1611

Intervention Type DRUG

MEN1611 oral dose administered twice daily for a continuous 28-day cycle

Trastuzumab

Intervention Type DRUG

Trastuzumab solution for infusion administered weekly via IV

Fulvestrant

Intervention Type DRUG

Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

Interventions

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MEN1611

MEN1611 oral dose administered twice daily for a continuous 28-day cycle

Intervention Type DRUG

Trastuzumab

Trastuzumab solution for infusion administered weekly via IV

Intervention Type DRUG

Fulvestrant

Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed invasive adenocarcinoma of the breast
* Known HER2+ breast cancer
* Advanced or metastatic breast cancer harbouring PIK3CA mutation on tissue sample
* \> 2 lines of anti-HER2 based regimens with at least 1 regimen with trastuzumab
* Radiological documented evidence of progressive disease
* Life expectancy ≥ 12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

Exclusion Criteria

* Previous treatment with PI3K inhibitors
* Brain metastases untreated, unless treated \> 4 weeks and only if clinically stable and not receiving corticosteroids
* History of clinically significant bowel disease
* ≥ grade 2 diarrhoea
* History of significant, uncontrolled, or active cardiovascular disease
* Any serious and/or unstable pre-existing psychiatric or neurologic illness or other conditions that could interfere with patient's safety
* Not controlled diabetes mellitus (glycated haemoglobin \[HbA1c\] \>7%) and fasting plasma glucose \>126 mg/dL
* Concurrent chronic treatment with steroids, as immunosuppressant, or another immunosuppressive agent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Menarini Group

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Martine Piccart, MD PhD

Role: STUDY_CHAIR

Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium

Locations

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Holy Cross Hospital Inc.

Fort Lauderdale, Florida, United States

Site Status

Detroit Clinical Research Center

Farmington Hills, Michigan, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Centre Georges François Leclerc

Dijon, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Institut Régional du Cancer de Montpellier

Montferrier-sur-Lez, , France

Site Status

ICO - Site René Gauducheau

Saint-Herblain, , France

Site Status

Institut Claudius Regaud Oncopole

Toulouse, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Azienda Ospedaliero Universitaria Mater Domini

Catanzaro, , Italy

Site Status

Istituto Clinico Humanitas

Milan, , Italy

Site Status

Istituto Europeo di Oncologia (IEO)

Milan, , Italy

Site Status

Ospedale San Raffaele

Milan, , Italy

Site Status

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status

Hospital General Universitario Gregorio Marañon

Madrid, , Spain

Site Status

START Madrid Fundacion Jimenez Diaz

Madrid, , Spain

Site Status

Hospital Clínico Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Hospital Universitario Virgen del Rocío

Seville, , Spain

Site Status

Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status

University College London Hospitals

London, , United Kingdom

Site Status

The Christie

Manchester, , United Kingdom

Site Status

Countries

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United States Belgium France Italy Spain United Kingdom

References

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Fiascarelli A, Merlino G, Capano S, Talucci S, Bisignano D, Bressan A, Bellarosa D, Carrisi C, Paoli A, Bigioni M, Tunici P, Irrissuto C, Salerno M, Arribas J, de Stanchina E, Scaltriti M, Binaschi M. Antitumor activity of the PI3K delta-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer. Breast Cancer Res Treat. 2023 May;199(1):13-23. doi: 10.1007/s10549-023-06895-2. Epub 2023 Mar 13.

Reference Type DERIVED
PMID: 36913051 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2017-004631-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MEN1611-01

Identifier Type: -

Identifier Source: org_study_id

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