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Advanced or Metastatic Breast CancerPhase 1B-PRECISE-01NCT03767335

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

A Phase 1 study testing MEN1611, Trastuzumab and Fulvestrant in people with Advanced or Metastatic Breast Cancer, run by Menarini Group at 27 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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 Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced or Metastatic Breast Cancer
What is being tested?
MEN1611, Trastuzumab and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
27 sitesin 6 countries
Study dates
13 Nov 2018to 23 Feb 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

27 sites in 6 countries.

27 sites in 6 countries

Spain7 sites

  • Hospital Clínic i Provincial de Barcelona

    Barcelona

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Centro Integral Oncologico Clara Campal

    Madrid

  • Hospital General Universitario Gregorio Marañon

    Madrid

  • START Madrid Fundacion Jimenez Diaz

    Madrid

  • Hospital Clínico Universitario Virgen de la Victoria

    Málaga

  • Hospital Universitario Virgen del Rocío

    Seville

Other trials in Spain

France6 sites

  • Centre Georges François Leclerc

    Dijon

  • Centre Oscar Lambret

    Lille

  • Institut Régional du Cancer de Montpellier

    Montferrier-sur-Lez

  • ICO - Site René Gauducheau

    Saint-Herblain

  • Institut Claudius Regaud Oncopole

    Toulouse

  • Institut Gustave Roussy

    Villejuif

Other trials in France

Italy4 sites

  • Azienda Ospedaliero Universitaria Mater Domini

    Catanzaro

  • Istituto Clinico Humanitas

    Milan

  • Istituto Europeo di Oncologia (IEO)

    Milan

  • Ospedale San Raffaele

    Milan

Other trials in Italy

United Kingdom4 sites

  • Velindre Cancer Centre

    Cardiff

  • Sarah Cannon Research Institute UK

    London

  • University College London Hospitals

    London

  • The Christie

    Manchester

Other trials in United Kingdom

United States3 sites

  • Detroit Clinical Research Center

    Farmington Hills, Michigan, 48334

  • Holy Cross Hospital Inc.

    Fort Lauderdale, Florida, 33308

  • Washington University

    St Louis, Missouri, 63130

Other trials in United States

Belgium3 sites

  • Cliniques Universitaires Saint-Luc

    Brussels

  • Institut Jules Bordet

    Brussels

  • UZ Leuven

    Leuven

Other trials in Belgium

About this study

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

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

Read the 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.

Being tested
MEN1611, Trastuzumab, Fulvestrant
Keywords
Advanced Breast Cancer, Metastatic Breast Cancer, PI3K inhibitor, HER2-positive
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MEN1611Drug

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

  • TrastuzumabDrug

    Trastuzumab solution for infusion administered weekly via IV

  • FulvestrantDrug

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

Study groups in NCT03767335
Study groupRoleWhat they receive
MEN1611ExperimentalMEN1611 + Trastuzumab +/- Fulvestrant
Receives: Drug: MEN1611; Drug: Trastuzumab; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    MTD was defined as the highest dose level at which no more than 1 participant experienced a DLT during the 28-day DLT assessment window.

    Measured: Up to 28 Days

  2. Number of Participants With DLTs of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    DLT was defined as the occurrence of any of the protocol defined adverse drug reactions (ADRs) related to the combination regimens or to MEN1611 alone and unrelated to the participants' underlying disease or concomitant medication occurring during 28 days after the first MEN1611 administration.

    Measured: Up to 28 days

  3. RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    RP2D was defined as the highest dose level in milligrams (mg) at which no more than 1 participant experienced a DLT during the DLT assessment window (28days), or the maximum dose judged to be tolerable.

    Measured: Up to 28 days

Secondary outcomes (6)

  1. Best Overall Response (BOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    BOR was defined as percentage of participants who had a best overall response to therapy of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) and was defined according to Response Evaluation Criteria in Solid Tumors version 1.1 assessment locally performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).

    Measured: Up to 3 years

  2. Objective Response Rate (ORR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    ORR was calculated as the sum of the Best Overall Response (BOR) of complete response (CR) and partial response (PR) rates. ORR was defined according to Response Evaluation Criteria in Solid Tumors version 1.1assessment performed using computed tomography scans or magnetic resonance imaging of the chest and abdomen (including pelvis and adrenal glands).

    Measured: Up to 3 years

  3. Disease Control Rate (DCR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    DCR was defined as percentage of participants whose disease shrank or remained stable over a certain time period and was calculated as the sum of the best overall response (BOR) rates of CR, PR and Stable Disease (SD) rates.

    Measured: Up to 3 years

  4. Duration of Response (DOR) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    DOR was defined as time from first occurrence of a BOR of PR, CR or SD as locally assessed, until the disease has been shown to progress following treatment. Participants with a previous response who did not show a relapse or die without recording a relapse were censored at their last available relapse-free tumour assessment date. Participants with only one tumour assessment after baseline showing progressive disease (PD) were not included in the calculation.

    Measured: Up to 3 years

  5. Progression-free Survival (PFS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    PFS was defined as the number of days between the first study treatment administration to the date of first documented disease progression as per local assessment, relapse or death from any cause. Responding participants and participants who were lost to follow-up were censored at their last tumour assessment date.

    Measured: Up to 3 years

  6. Overall Survival (OS) of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    OS was defined as the number of days between the first study treatment administration and death from any cause. Participants still alive who had withdrawn from the study were censored using the latest among end of study and follow-up dates. Drop-out participants were considered censored and the last available date in which the participant was known to be alive were used for calculation.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2018
  2. Study start13 Nov 2018
  3. Primary completion23 Feb 2024
  4. Study completion23 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03767335
Sponsor's protocol ID
MEN1611-01
Other IDs
2017-004631-36, 2017
Acronym
B-PRECISE-01
Status last verified
Apr 2025
First submitted
5 Dec 2018
Last updated
26 Jun 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36913051

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MEN1611, Trastuzumab and Fulvestrant in people with Advanced or Metastatic Breast Cancer, run by Menarini Group at 27 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Spain, France, Italy, United Kingdom, United States and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant (time frame: Up to 28 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03767335, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2025.

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