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

Advanced or Metastatic Breast Cancer Clinical Trial

— B-PRECISE-01  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03767335
• Other study ID #: MEN1611-01
• Secondary ID: 2017-004631-36
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 19, 2018
• Est. completion date: December 21, 2023

Study information

• Verified date: May 2023
• Source: Menarini Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 62
• Est. completion date: December 21, 2023
• Est. primary completion date: December 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced or Metastatic Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• MEN1611
MEN1611 oral dose administered twice daily for a continuous 28-day cycle
• Trastuzumab
Trastuzumab solution for infusion administered weekly via IV
• Fulvestrant
Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Leuven	Leuven
France	Centre Georges François Leclerc	Dijon
France	Centre Oscar Lambret	Lille Cedex
France	Institut Régional du Cancer de Montpellier	Montferrier Sur Lez
France	ICO - Site René Gauducheau	Saint-Herblain
France	Institut Claudius Regaud Oncopole	Toulouse
France	Institut Gustave Roussy	Villejuif cedex
Italy	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro
Italy	Istituto Clinico Humanitas	Milan
Italy	Istituto Europeo di Oncologia (IEO)	Milan
Italy	Ospedale San Raffaele	Milan
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Centro Integral Oncologico Clara Campal	Madrid
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	START Madrid Fundacion Jimenez Diaz	Madrid
Spain	Hospital Clínico Universitario Virgen de la Victoria	Málaga
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	Sarah Cannon Research Institute UK	London
United Kingdom	University College London Hospitals	London
United Kingdom	The Christie	Manchester
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	Holy Cross Hospital Inc.	Fort Lauderdale	Florida
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Menarini Group

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D)		28 Days
Secondary	Treatment emergent adverse events (TEAEs)		2 years
Secondary	Progression Free Survival		2 years
Secondary	Overall Survival		2 years