PhIb BKM120 or BEZ235+Endocrine Treatment in Post-Menopausal Patients With Hormone Receptor + Metastatic Breast Cancer
A Phase Ib Trial of BKM120 (a PI3K Inhibitor) or BEZ235 (a PI3K/mTOR Inhibitor) in Combination With Endocrine Therapy in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer
1 other identifier
interventional
72
1 country
6
Brief Summary
This is an open-label phase Ib multi-institution trial that evaluates the safety profile/tolerability and preliminary anti-tumor effect of BKM120 (a PI3K inhibitor) and endocrine therapy combination and BEZ235 (a PI3K/ mTOR inhibitor) and endocrine therapy combination in postmenopausal patients with hormone receptor-positive metastatic breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Nov 2010
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2010
CompletedFirst Submitted
Initial submission to the registry
November 23, 2010
CompletedFirst Posted
Study publicly available on registry
November 25, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2016
CompletedJuly 25, 2016
July 1, 2016
2.1 years
November 23, 2010
July 22, 2016
Conditions
Outcome Measures
Primary Outcomes (1)
Maximum Tolerated Dose of BKM120 or BEZ235 given in combination with endocrine therapy
The maximum tolerated dose for each of the arms will be defined as the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels. The first cohort of patients (3 patients) in each arm will be started at dose level 1, and each patient will be observed for 4 weeks on the specified dose.
at 4 weeks
Secondary Outcomes (2)
Number of Patients with Progression-free survival (PFS)
4 weeks after off-treatment date
Response Rate (RR)
4 weeks after off-treament date
Study Arms (3)
BEZ235 + Letrozole
EXPERIMENTALBKM120 + Letrozole
EXPERIMENTALIntermittent BKM120 + Letrozole
EXPERIMENTALInterventions
* Dose level 1: 400mg PO BID * Dose level -1: 400mg PO in AM and 200mg PO in PM * Dose level -2: 200mg PO BID
* Dose Level 1: BKM120, 100 mg PO daily * Dose level -1: BKM120, 80 mg PO daily * Dose Level -2: BKM120, 60 mg PO daily
All levels: 2.5mg/day PO
* Dose Level 1: BKM120, 100 mg PO from Mondays through Fridays, weekly * Dose level -1: BKM120, 80 mg PO from Mondays through Fridays, weekly * Dose Level -2: BKM120, 60 mg PO from Mondays through Fridays, weekly
Eligibility Criteria
You may qualify if:
- Patients must provide informed written consent.
- Patients must be \>/= 18 years of age.
- ECOG performance status 0-1.
- Clinical stage IV invasive mammary carcinoma, ER-positive and/or PR-positive by immunohistochemistry (IHC). Patients may have either measurable or nonmeasurable disease, both are allowed.
- Patients whose breast cancers are also HER2-overexpressed (IHC 3+ or FISHpositive)need to have had previous treatment exposure to trastuzumab (Herceptin®)
- Prior endocrine therapy (any) is allowed. There is not limit on lines of prior treatment in the metastatic setting.
- Patients must have available tissue (archived formalin-fixed paraffin embedded blocks (FFPB) or fresh frozen tissue from original diagnosis or metastatic setting) for correlative studies. Tissue needs to be submitted at the time of registration. Patients will not be able to start study drugs without tissue availability.
- Life expectancy \>/= 6 months
- Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
- ANC \>/= 1500/mm3
- Platelet count \>/= 100,000/mm3
- HgB \>/= 9 g/dL
- Creatinine \</= 1.5X upper limits of normal
- INR \</= 2Total serum bilirubin \</= 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin \</= 3.0 x ULN, with direct bilirubin \</= 1.5 x ULN)
- AST and ALT \</= 3 x ULN (or \</= 5.0 x ULN if hepatic metastases are present)
- +11 more criteria
You may not qualify if:
- Locally recurrent resectable breast cancer.
- Any kind of malabsorption syndrome significantly affecting gastrointestinal function.
- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication, as well as recovered from toxicity (to \</= than grade 1, except for alopecia) induced by previous treatments. Any investigational drugs should be discontinued 2 weeks prior to the first dose of study medication.
- Prior therapy with a PI3K specific inhibitor. Prior use of Akt or mTOR inhibitors are allowed.
- Use of any of the drugs (prohibited concomitant medications)
- Patients with the following mood disorders as judged by the Investigator or a psychiatrist:
- medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
- \>/= CTCAE grade 3 anxiety
- Meets the cut-off score of \>/= 10 in the PHQ-9 or a cut-off of \>/= 15 in the GAD-7 mood scale, respectively, or selects a positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment
- Uncontrolled intercurrent illness including, but not limited to:
- ongoing or active infection requiring parenteral antibiotics
- impairment of lung function (COPD \> grade 2, lung conditions requiring oxygen therapy)
- symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)
- Left Ventricular Ejection Fraction (LVEF) \< 50%
- unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
University of Alabama
Birmingham, Alabama, United States
Massachusetts General Hospital, Dana Farber Cancer Center
Boston, Massachusetts, 02114, United States
Columbia University Medical Center
New York, New York, United States
Vanderbilt Cool Springs
Nashville, Tennessee, 37067, United States
Vanderbilt Breast Center One Hundred Oaks
Nashville, Tennessee, 37204, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ingrid Mayer, MD
Vanderbilt-Ingram Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist
Study Record Dates
First Submitted
November 23, 2010
First Posted
November 25, 2010
Study Start
November 1, 2010
Primary Completion
December 1, 2012
Study Completion
May 1, 2016
Last Updated
July 25, 2016
Record last verified: 2016-07