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Completed

NCT Number: NCT03767335

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

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

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Key information

Conditions

Advanced or Metastatic Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Cliniques Universitaires Saint-Luc, Brussels, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

MEN1611

Drug

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

Trastuzumab

Drug

Trastuzumab solution for infusion administered weekly via IV

Fulvestrant

Drug

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

Primary outcomes

  1. MTD of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    Time frame: Up to 28 Days

    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.

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

    Time frame: Up to 28 days

    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.

  3. RP2D of MEN1611 in Combination With Trastuzumab ± Fulvestrant

    Time frame: Up to 28 days

    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.

Secondary outcomes

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

    Time frame: Up to 3 years

    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).

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

    Time frame: Up to 3 years

    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).

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

    Time frame: Up to 3 years

    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.

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

    Time frame: Up to 3 years

    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.

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

    Time frame: Up to 3 years

    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.

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

    Time frame: Up to 3 years

    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.

Sponsors and collaborators

Lead sponsor

Menarini Group

Industry

Registry information

Official study 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

Acronym: B-PRECISE-01

Important dates

Study start
2018
Primary completion
2024
Study completion
2024
First posted
Dec 6, 2018
Registry last updated
Jun 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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