BYL719 + T-DM1 in HER2(+) Metastatic Breast Cancer Pts Who Progress on Prior Trastuzumab & Taxane Tx
The purpose of this study is to see whether a combination of two different drugs - trastuzumab-MCC-DM1 (T-DM1) and BYL719 is safe, and if it might be effective in treating metastatic breast cancer. T-DM1 is a type of drug that contains an antibody (trastuzumab) linked to chemotherapy. The antibody in T-DM1 targets a marker on breast cancer cells called HER2, which allows the drug to go directly to the cancer cells. The use of T-DM1 in this study is considered standard treatment for the type of cancer in this study. Participants in this study have already been treated with trastuzumab and chemotherapy in the past, and their cancer has gotten worse in spite of those treatments. BYL719 is an oral drug (taken by mouth) that the researchers think may help T-DM1 to work better.
HER2-positive Breast Cancer
Recurrent Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Drug: PI3K inhibitor BYL719
Biological: ado-trastuzumab emtansine
Other: pharmacological study
Other: laboratory biomarker analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of BYL719 and Trastuzumab-MCC-DM1 in HER2-Positive Metastatic Breast Cancer Patients With Progression on Prior Trastuzumab and Taxane-Based Therapy|
- Determine the Dose Limiting Toxicity (DLT) of dose-escalating BYL719 in combination with T-DM1 [ Time Frame: The 1st 21 days ] [ Designated as safety issue: Yes ]The DLT of BYL719 in combination with T-DM1 will be assessed during the first 21 days (1 cycle=21 days).
- Determine the Maximum Tolerated Dose (MTD) of BYL719 in combination with T-DM1 [ Time Frame: The 1st 21 days ] [ Designated as safety issue: Yes ]The safety of BYL719 in combination with T-DM1 will be assessed during the first 21 days (1 cycle=21 days) which will assist in providing the MTD. More specifically, Adverse Events including dose limiting toxicities (DLT), changes in physical findings, or clinical laboratory results as well as cardiac toxicity (changes in cardiac function, which will be measured by use of echocardiogram or MUGA scan) will be evaluated while patient is on study drug.
- Blood will be collected to determine how the body responds to study drugs [ Time Frame: Day 1, 8, and 15 of Cycles 1, 2, and 3, then every 3 Cycles while the patient remains on study (e.g., Cycles 6, 9, 12, until completion of study) ] [ Designated as safety issue: No ]Bloodwork will be analyzed to evaluate pharmacokinetics
- Progression-Free Survival (PFS) [ Time Frame: Every 3 months up to 1 year after discontinuation of the study drugs ] [ Designated as safety issue: No ]PFS will be assessed every 3 months up to 1 year after discontinuation of the study drugs
- Objective Response Rate (ORR) [ Time Frame: Every 2 cycles up to 1 year after discontinuation of the study drugs ] [ Designated as safety issue: No ]ORR will be assessed every 2 cycles (every 6 weeks) with imaging (CT chest/abdomen/pelvis and bone scan, or PET/CT).
- Alteration (mutation or amplification) of the PIK3CA gene and decrease of PTEN expression [ Time Frame: Baseline OR during Cycle 3 ] [ Designated as safety issue: No ]Patients tumor tissue collected during biopsy will be evaluated to see if the study drugs are efficacious on patients who have this alteration.
- Akt/mTOR downstream markers [ Time Frame: Baseline OR during Cycle 3 ] [ Designated as safety issue: No ]Patients tumor tissue collected during biopsy will be evaluated to assess the relationship between expression and efficacy of study drugs.
|Study Start Date:||February 2014|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (PI3K inhibitor BYL719, ado-trastuzumab emtansine)
Patients receive PI3K inhibitor BYL719 PO daily on days 1-21 and ado-trastuzumab emtansine IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: PI3K inhibitor BYL719
Other Names:Biological: ado-trastuzumab emtansine
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Optional correlative studies
I. Determine safety, tolerability, feasibility, and the maximum-tolerated dose (MTD) of dose-escalating BYL719 in combination with ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer (MBC) after progression on trastuzumab and taxane-based therapy.
I. Evaluate pharmacokinetics (PK) of BYL719 administered in combination with T-DM1.
II. Assess any preliminary evidence of efficacy of BYL719 and T-DM1 in combination in patients with HER2-positive MBC.
I. Explore efficacy in patients whose tumors have an alteration (mutation or amplification) of the PIK3CA gene and decrease of phosphatase and tensin homolog gene (PTEN) expression. (Optional) II. Examine other v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) downstream markers by immunohistochemistry. (Optional)
OUTLINE: This is a dose-escalation study of PI3K inhibitor BYL719.
Patients receive PI3K inhibitor BYL719 orally (PO) daily on days 1-21 and ado-trastuzumab emtansine (T-DM1) intravenously (IV) over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity, or at the discretion of the treating physician.
After completion of study treatment, patients are followed up every 3 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02038010
|Contact: Study Coordinator||(312)firstname.lastname@example.org|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Sarika Jain, MD 312-695-0990|
|Principal Investigator: Sarika Jain|
|Principal Investigator:||Sarika Jain||Northwestern University|