MEN1611 With Trastuzumab (+/- Fulvestrant) in Metastatic Breast Cancer (B-PRECISE-01)

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: MEN1611; Drug: Trastuzumab; Drug: Fulvestrant

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Institut Jules Bordet
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium
    • UZ Leuven
• France
  • Dijon, France
    • Centre Georges François Leclerc
  • Lille Cedex, France
    • Centre Oscar Lambret
  • Montferrier Sur Lez, France
    • Institut Régional du Cancer de Montpellier
  • Saint-Herblain, France
    • ICO - Site René Gauducheau
  • Toulouse, France
    • Institut Claudius Regaud Oncopole
  • Villejuif cedex, France
    • Institut Gustave Roussy
• Italy
  • Catanzaro, Italy
    • Azienda Ospedaliero Universitaria Mater Domini
  • Milan, Italy
    • Ospedale San Raffaele
  • Milan, Italy
    • Istituto Clinico Humanitas
  • Milan, Italy
    • Istituto Europeo di Oncologia (IEO)
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Clínic i Provincial de Barcelona
  • Madrid, Spain
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain
    • START Madrid Fundacion Jimenez Diaz
  • Málaga, Spain
    • Hospital Clinico Universitario Virgen de la Victoria
  • Sevilla, Spain
    • Hospital Universitario Virgen Del Rocio
• United Kingdom
  • Cardiff, United Kingdom
    • Velindre Cancer Centre
  • London, United Kingdom
    • University College London Hospitals
  • London, United Kingdom
    • Sarah Cannon Research Institute UK
  • Manchester, United Kingdom
    • The Christie
• United States
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital Inc.
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Detroit Clinical Research Center
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MEN1611; MEN1611 + Trastuzumab +/- Fulvestrant	Drug: MEN1611; MEN1611 oral dose administered twice daily for a continuous 28-day cycle; Drug: Trastuzumab; Trastuzumab solution for infusion administered weekly via IV; Drug: Fulvestrant; Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D)	28 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression Free Survival	2 years
Overall Survival	2 years
Treatment emergent adverse events (TEAEs)	2 years

Collaborators and Investigators

• Sponsor: Menarini Group
• Investigators: Study Chair: Martine Piccart, MD PhD, Institute Jules Bordet - Boulevard De Waterloo 125 - B-1000 Brussels, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2018
• Primary Completion (Anticipated): December 21, 2023
• Study Completion (Anticipated): December 21, 2023

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 23, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Breast Cancer; Metastatic Breast Cancer; HER2-positive; PI3K inhibitor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Trastuzumab; Fulvestrant
• Other Study ID Numbers: MEN1611-01; 2017-004631-36 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No