Clinical trial NCT03767335: MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer
Official title: Open-label, Multicentre, Phase Ib Dose-escalation Study of MEN1611, a PI3K Inhibitor Combined With Trastuzumab With or Without Fulvestrant, in Subjects With PIK3CA Mutated HER2 Positive Locally Recurrent Unresectable (Advanced) or Metastatic (a/m) Breast Cancer Progressed to Anti-HER2 Based Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced or Metastatic Breast Cancer
Keywords: Advanced Breast Cancer
Metastatic Breast Cancer
PI3K inhibitor
HER2-positive
Lead sponsor: Menarini Group
Sponsor class: INDUSTRY
First posted: 2018-12-06
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations
Primary purpose: TREATMENT

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.

Eligibility criteria: Main 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

Main 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D)
timeFrame: 28 Days
Secondary outcomes:
measure: Treatment emergent adverse events (TEAEs)
timeFrame: 2 years
measure: Progression Free Survival
timeFrame: 2 years
measure: Overall Survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital Inc.
state: Florida
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lille Cedex
country: France
facility: Centre Oscar Lambret
city: Montferrier Sur Lez
country: France
facility: Institut Régional du Cancer de Montpellier
city: Saint-Herblain
country: France
facility: ICO - Site René Gauducheau
city: Toulouse
country: France
facility: Institut Claudius Regaud Oncopole
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Milan
country: Italy
facility: Istituto Clinico Humanitas
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: START Madrid Fundacion Jimenez Diaz
city: Málaga
country: Spain
facility: Hospital Clínico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
affiliation: Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium
name: Martine Piccart, MD PhD
role: STUDY_CHAIR
References: