MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer
- Conditions
- Advanced or Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT03767335
- Lead Sponsor
- Menarini Group
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
- 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
Main
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description MEN1611 MEN1611 MEN1611 + Trastuzumab +/- Fulvestrant MEN1611 Trastuzumab MEN1611 + Trastuzumab +/- Fulvestrant MEN1611 Fulvestrant MEN1611 + Trastuzumab +/- Fulvestrant
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D) 28 Days
- Secondary Outcome Measures
Name Time Method Progression Free Survival 2 years Overall Survival 2 years Treatment emergent adverse events (TEAEs) 2 years
Trial Locations
- Locations (27)
Holy Cross Hospital Inc.
🇺🇸Fort Lauderdale, Florida, United States
UZ Leuven
🇧🇪Leuven, Belgium
Detroit Clinical Research Center
🇺🇸Farmington Hills, Michigan, United States
Istituto Europeo di Oncologia (IEO)
🇮🇹Milan, Italy
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Centre Oscar Lambret
🇫🇷Lille Cedex, France
Washington University
🇺🇸Saint Louis, Missouri, United States
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Clínico Universitario Virgen de la Victoria
🇪🇸Málaga, Spain
ICO - Site René Gauducheau
🇫🇷Saint-Herblain, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
Institut Régional du Cancer de Montpellier
🇫🇷Montferrier Sur Lez, France
University College London Hospitals
🇬🇧London, United Kingdom
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clínic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
The Christie
🇬🇧Manchester, United Kingdom
START Madrid Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Azienda Ospedaliero Universitaria Mater Domini
🇮🇹Catanzaro, Italy
Ospedale San Raffaele
🇮🇹Milan, Italy
Istituto Clinico Humanitas
🇮🇹Milan, Italy
Institut Gustave Roussy
🇫🇷Villejuif cedex, France
Institut Claudius Regaud Oncopole
🇫🇷Toulouse, France
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium