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

Menarini

Status and phase: Completed; Phase 1

Conditions: Advanced or Metastatic Breast Cancer

Treatments: Drug: Fulvestrant; Drug: MEN1611; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03767335

2017-004631-36 (EudraCT Number)

MEN1611-01

Details and patient eligibility

About

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

Full 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.

Enrollment: 62 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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62 participants in 1 patient group

MEN1611

Experimental group

Description:

MEN1611 + Trastuzumab +/- Fulvestrant

Treatment:

Drug: Trastuzumab

Drug: MEN1611

Drug: Fulvestrant