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

Sponsor

Menarini Group (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03767335

Collaborator

(none)

Enrollment

Locations

Arm

48.4

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic Breast Cancer	Drug: MEN1611 Drug: Trastuzumab Drug: Fulvestrant	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

Step 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populationsStep 1 Dose escalation / Step 2 Cohort expansion in two selected breast cancer sub-populations

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 19, 2018

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Maximum Tolerated Dose (MTD) and Recommended Phase 2 dose (RP2D) [28 Days]

Secondary Outcome Measures

Treatment emergent adverse events (TEAEs) [2 years]
Progression Free Survival [2 years]
Overall Survival [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Holy Cross Hospital Inc.	Fort Lauderdale	Florida	United States	33308
2	Detroit Clinical Research Center	Farmington Hills	Michigan	United States	48334
3	Washington University	Saint Louis	Missouri	United States	63130
4	Cliniques Universitaires Saint-Luc	Brussels		Belgium
5	Institut Jules Bordet	Brussels		Belgium
6	UZ Leuven	Leuven		Belgium
7	Centre Georges François Leclerc	Dijon		France
8	Centre Oscar Lambret	Lille Cedex		France
9	Institut Régional du Cancer de Montpellier	Montferrier Sur Lez		France
10	ICO - Site René Gauducheau	Saint-Herblain		France
11	Institut Claudius Regaud Oncopole	Toulouse		France
12	Institut Gustave Roussy	Villejuif cedex		France
13	Azienda Ospedaliero Universitaria Mater Domini	Catanzaro		Italy
14	Istituto Clinico Humanitas	Milan		Italy
15	Istituto Europeo di Oncologia (IEO)	Milan		Italy
16	Ospedale San Raffaele	Milan		Italy
17	Hospital Clínic i Provincial de Barcelona	Barcelona		Spain
18	Hospital Universitari Vall d'Hebron	Barcelona		Spain
19	Centro Integral Oncologico Clara Campal	Madrid		Spain
20	Hospital General Universitario Gregorio Marañon	Madrid		Spain
21	START Madrid Fundacion Jimenez Diaz	Madrid		Spain
22	Hospital Clínico Universitario Virgen de la Victoria	Málaga		Spain
23	Hospital Universitario Virgen del Rocío	Sevilla		Spain
24	Velindre Cancer Centre	Cardiff		United Kingdom
25	Sarah Cannon Research Institute UK	London		United Kingdom
26	University College London Hospitals	London		United Kingdom
27	The Christie	Manchester		United Kingdom