BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer
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ClinicalTrials.gov Identifier: NCT01791478 |
Recruitment Status :
Active, not recruiting
First Posted : February 15, 2013
Last Update Posted : October 8, 2020
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Tracking Information | ||||
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First Submitted Date ICMJE | February 11, 2013 | |||
First Posted Date ICMJE | February 15, 2013 | |||
Last Update Posted Date | October 8, 2020 | |||
Study Start Date ICMJE | April 2013 | |||
Actual Primary Completion Date | December 2014 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Maximum tolerated dose of BYL719 in combination with letrozole [ Time Frame: 4 weeks ] Highest dose of BYL719 tested in which a DLT is experienced by 0 out of 3 or 1 of 6 patients, based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
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Original Primary Outcome Measures ICMJE | Same as current | |||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer | |||
Official Title ICMJE | 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 | |||
Brief Summary | 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 | |||
Detailed Description | 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:
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. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 1 | |||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (PI3K inhibitor BYL719, letrozole)
Patients receive PI3K inhibitor BYL719 PO QD and letrozole PO QD. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Not Provided | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
46 | |||
Original Estimated Enrollment ICMJE |
30 | |||
Estimated Study Completion Date ICMJE | September 2021 | |||
Actual Primary Completion Date | December 2014 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria
Exclusion Criteria
Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards age or race in the clinical trial outlined. This trial is open to the accrual of women. |
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01791478 | |||
Other Study ID Numbers ICMJE | VICC BRE 12101 NCI-2013-00102 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Responsible Party | Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center | |||
Study Sponsor ICMJE | Vanderbilt-Ingram Cancer Center | |||
Collaborators ICMJE | National Cancer Institute (NCI) | |||
Investigators ICMJE |
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PRS Account | Vanderbilt-Ingram Cancer Center | |||
Verification Date | October 2020 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |