This research study is a way of gaining new knowledge about the combination of Taselisib with other drugs in the treatment of metastatic breast cancer. Taselisib is an investigational drug which works by blocking a protein called PI3K (phosphoinositide 3-kinase) that helps cancer cells grow. This drug has been used in laboratory experiments and information from these studies suggests that this drug may help to prevent or slow the growth of cancer cells. The main purpose of this study is to find the appropriate dose of Taselisib to be used with other drugs in further clinical studies. This is an open-label, 3+3 dose-escalation phase Ib study to identify the Maximum Tolerated Dose(s) (MTD) and to identify the recommended phase 2 dose (RP2D) of Taselisib. This study will be conducted in 4 separate arms. (A-D).
This study is divided in two parts, a combination dose finding escalation part (Part 1) and a dose combination expansion part (Part 2). Participants will enter only one Part (either 1 or 2) and receive study drugs from only one combindation of study drugs, know as arms, as assigned by the main study physician. The study includes four different arms as listed below: * Arm A: Taselisib with Trastuzumab emtansine (also called T-DM1) * Arm B: Taselisib with Trastuzumab emtansine and Pertuzumab * Arm C: Taselisib with Pertuzumab and Trastuzumab * Arm D: Taselisib with Pertuzumab, Trastuzumab, and Paclitaxel Part 1: Since we are looking for the highest dose of Taselisib that can be administered safely without severe or unmanageable side effects in participants that have breast cancer, not everyone who participates in Part 1 of this research study will receive the same dose of the Taselisib. The dose participants get will depend on the number of participants who have been enrolled in the study before and how well they have tolerated their doses. Each combination dose will only be given to a group of 3 - 6 participants. The results from each group will be reviewed and depending on the results, a different combination dose or schedule may be investigated in the next group of participants or the same combination dose taken by a participant may be repeated with the next group of participants to investigate these results further (a different schedule means that instead of taking doses once every day, participants may take them only on some days in the week). Part 2: The doses in this part will be based on the best combination doses from Part 1. This part will look at the potential side effects and see how your cancer responds to the drug.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
68
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Maximum Tolerated Dose (MTD) of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Time frame: 28 Days
Clinical Benefit Rate (CBR) for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Defined as complete response (CR) + partial response (PR) + stable disease (SD) using RECIST 1.1
Time frame: > or = 6 Months
Progression Free Survival (PFS) for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Defined as the time from the date of the first dose of study treatment until the date of first documentation of progressive disease (PD) or death from any cause (whichever occurs first)
Time frame: 2 Years
Overall Survival for efficacy of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Defined as the time from the date of the first dose of study treatment until the date of death from any cause
Time frame: 2 Years
Occurrence of AEs and SAEs during treatment with Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Defined with CTCAE version 4.0
Time frame: 2 Years
Occurrence of dose delays or holds
Defined as a delay or hold of one of the study agents for more than 7 days
Time frame: More than 7 Days
Occurrence of dose reductions
Time frame: 2 Years
Dose Limiting Toxicity of Taselisib in combination with anti-HER2 therapy(ies) and/or paclitaxel.
Defined as a toxicity within the DLT Assessment Window.
Time frame: 28 Days
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