Stage IV Breast Cancer Clinical Trial
Official title:
A Phase Ib Trial of BYL719 (an α-Specific PI3K Inhibitor) in Combination With Endocrine Therapy in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer
This phase I trial studies the side effects and best dose of the PI3K inhibitor BYL719 when given together with letrozole in treating patients with hormone receptor-positive metastatic breast cancer. The PI3K inhibitor BYL719 may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving the PI3K inhibitor BYL719 together with letrozole may kill more tumor cells
PRIMARY OBJECTIVE: To determine the safety and tolerability of BYL719 given in combination with endocrine therapy in post-menopausal patients with hormone receptor-positive metastatic breast cancer by determining: I. Dose limiting toxicities (DLTs) during the first 4 weeks of treatment (cycle 1). II. Maximum tolerated dose (MTD) of BYL719 (PI3K inhibitor BYL719) given in combination with letrozole. III. Highest tolerated dose - ability to tolerate BYL719 with letrozole for a total of 8 weeks without development of: - Hyperglycemia (fasting glucose > 200 mg/dL) for more than 2 weeks in a row despite optimal medical treatment - CTC Grade 3 or > rash for more than 2 weeks in a row despite optimal medical treatment - CTC Grade 2 or > GI toxicity for more than 2 weeks in a row despite optimal medical treatment - CTC Grade 2 or > serum creatinine, bilirubin, AST, ALT elevation from baseline for more than 2 weeks in a row despite optimal medical treatment SECONDARY OBJECTIVES: To determine the anti-tumor effect of the combinations of endocrine therapy with BYL719 in post-menopausal patients with hormone receptor-positive metastatic breast cancer by assessing: I. Progression free survival (PFS). II. Objective response rate (ORR). III. Clinical benefit rate (complete response [CR]+partial response [PR]+stable disease [SD] >= 6 months). EXPLORATORY OBJECTIVES: I. Pharmacokinetics of BYL719 in combination with letrozole: Plasma concentration-time profiles and derived basic pharmacokinetic (PK) parameters of BYL719 and letrozole, including but not limited to area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-tlast), AUC curve to infinite time (AUC0-inf), maximum observed concentration (Cmax), time to peak concentration (Tmax), clearance over bioavailability (CL/F), apparent volume of distribution (Vz/F) and the terminal half-life (t1/2) and other PK parameters if deemed appropriate. II. Correlation of response with alterations of the PI3K pathway: Mutational analysis of PIK3CA (exons 9 and 20), phosphatase and tensin homolog (PTEN), and AKT1 in formalin-fixed paraffin blocks (FFPB) from previous surgeries or fresh-frozen biopsies (if available) on all patients enrolled in the trial. OUTLINE: This is an open-label phase Ib dose-escalation study of the PI3K inhibitor BYL719 in combination with letrozole in post-menopausal patients with ER+ metastatic breast cancer. Patients receive BYL719 orally (PO) once daily (QD) and letrozole PO QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 4 weeks. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01987726 -
Comprehensive Gene Sequencing in Guiding Treatment Recommendations Patients With Metastatic or Recurrent Solid Tumors
|
||
Completed |
NCT01881230 -
Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)
|
Phase 2/Phase 3 | |
Terminated |
NCT01918306 -
GDC-0941 and Cisplatin in Treating Patients With Androgen Receptor-Negative Triple Negative Metastatic Breast Cancer
|
Phase 1/Phase 2 | |
Terminated |
NCT01705340 -
Akt Inhibitor MK2206, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With Locally Advanced or Metastatic HER2-Positive Breast , Gastric, or Gastroesophageal Cancer That Cannot Be Removed By Surgery
|
Phase 1 | |
Terminated |
NCT01222377 -
Endoscopic Breast Surgery in Treating Patients With Breast Cancer
|
N/A | |
Completed |
NCT00602043 -
F-18 16 Alpha-Fluoroestradiol-Labeled Positron Emission Tomography in Predicting Response to First-Line Hormone Therapy in Patients With Stage IV Breast Cancer
|
Phase 2 | |
Completed |
NCT00244881 -
A Phase II Study of AZD2171 in Breast Cancer Stage IV (10006202)
|
Phase 2 | |
Completed |
NCT00100750 -
Tipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT00425672 -
ONTAK® in Treating Patients With Advanced Breast Cancer That Did Not Respond to Previous Treatment
|
Phase 1/Phase 2 | |
Completed |
NCT00096109 -
Tanespimycin in Treating Women With Refractory Locally Advanced or Metastatic Breast Cancer
|
Phase 2 | |
Completed |
NCT00096434 -
Sorafenib in Treating Patients With Metastatic Breast Cancer
|
Phase 2 | |
Completed |
NCT00057941 -
Anastrozole and ZD1839 Compared With Fulvestrant and ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer
|
Phase 2 | |
Terminated |
NCT02892734 -
Ipilimumab and Nivolumab in Treating Patients With Recurrent Stage IV HER2 Negative Inflammatory Breast Cancer
|
Phase 2 | |
Recruiting |
NCT03213041 -
Pembrolizumab and Carboplatin in Treating Patients With Circulating Tumor Cells Positive Metastatic Breast Cancer
|
Phase 2 | |
Completed |
NCT02015559 -
Mucoadhesive Oral Wound Rinse in Preventing and Treating Stomatitis in Patients With ER- or PR-Positive Metastatic or Locally Recurrent Breast Cancer That Cannot be Removed by Surgery Receiving Everolimus
|
Phase 2 | |
Completed |
NCT02728596 -
S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)
|
N/A | |
Completed |
NCT03364348 -
4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer
|
Phase 1 | |
Completed |
NCT02897375 -
Palbociclib With Cisplatin or Carboplatin in Advanced Solid Tumors
|
Phase 1 | |
Completed |
NCT01672684 -
Phase I: At-Home Support for Rural Women Using Group Video Calling
|
Phase 1 | |
Terminated |
NCT01217411 -
RO4929097 and Whole-Brain Radiation Therapy or Stereotactic Radiosurgery in Treating Patients With Brain Metastases From Breast Cancer
|
Phase 1 |