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
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
MEN1611 oral dose administered twice daily for a continuous 28-day cycle
Trastuzumab solution for infusion administered weekly via IV
Fulvestrant solution for injection administered monthly via IM (only for HR-positive postmenopausal women)
Holy Cross Hospital Inc.
Fort Lauderdale, Florida, United States
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.
Time frame: Up to 28 Days
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.
Time frame: Up to 28 days
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.
Time frame: Up to 28 days
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).
Time frame: Up to 3 years
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).
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Detroit Clinical Research Center
Farmington Hills, Michigan, United States
Washington University
St Louis, Missouri, United States
Cliniques Universitaires Saint-Luc
Brussels, Belgium
Institut Jules Bordet
Brussels, Belgium
UZ Leuven
Leuven, Belgium
Centre Georges François Leclerc
Dijon, France
Centre Oscar Lambret
Lille, France
Institut Régional du Cancer de Montpellier
Montferrier-sur-Lez, France
ICO - Site René Gauducheau
Saint-Herblain, France
...and 17 more locations
Time frame: Up to 3 years
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.
Time frame: Up to 3 years
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.
Time frame: Up to 3 years
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.
Time frame: Up to 3 years
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.
Time frame: Up to 3 years