STAR Cape+BKM120 MBC With Brain Met
This is a study to determine the safety and effectiveness of BKM120 plus capecitabine in breast cancer patients with brain metastases.
Both capecitabine and BMK120 have previously shown activity in patients with breast cancer. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with metastatic breast cancer (MBC).
Metastatic Breast Cancer
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Multicenter Single-arm Study of BKM120 Plus Capecitabine for Breast Cancer Patients With Brain Metastases|
- clinical benefit rate (CBR) [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: No ]To determine the clinical benefit rate (CBR) based on local investigator assessment associated with BKM120 once daily plus capecitabine (1000 mg/m2 PO BID 14 days on/7 days off) in patients with metastatic breast cancer with a brain metastasis at least 5mm in size following whole brain radiation therapy (WBRT) and that has not progressed following WBRT. An exploratory analysis will be conducted of patients enrolled on study who have evidence of disease progression following WBRT. Clinical benefit rate is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) in the CNS lasting at least 24 weeks based on local investigator assessment.
- Objective Response Rate (ORR) [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: No ]To assess ORR associated with BKM120 plus capecitabine in the central nervous system based on local investigator assessment
- Median time to progression [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: No ]To assess median time to progression (TTP) associated with BKM120 plus capecitabine.
- Median Overall Survival [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: No ]To determine median overall survival (OS) associated with BKM120 plus capecitabine.
- Number of Adverse Events [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: Yes ]To characterize the safety and tolerability of BKM120 plus capecitabine, with or without trastuzumab
- Median time to deterioration of neurologic function [ Time Frame: until end of study (4 years) ] [ Designated as safety issue: Yes ]To assess median time to deterioration of neurologic function based on answers to questionnaires.
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
Experimental: BKM120 plus Capecitabine
BKM120 will be administered at a dose of 100 mg orally (PO) daily. Capecitabine will be administered at a dose of 1000 mg/m2 orally (PO) twice a day (rounded down to the nearest 500 mg pill) 14 days on and 7 days off.
For patients with HER2+ MBC only, standard every 3-weekly trastuzumab (6 mg/kg IV) will be added to the capecitabine/BKM120.
Other Name: buparlisibDrug: capecitabine
Other Name: XelodaDrug: Trastuzumab
Other Name: Herceptin
This is a Phase 2, multicenter, single-arm study to determine the safety and efficacy of BKM120 plus capecitabine in breast cancer patients with brain metastases. 40 patients will be included, who have either ER+/HER2-, HER2+ or triple negative breast cancer..
The Graded Prognostic Assessment (GPA) is a recently developed, validated prognostic score for patients with brain metastases. The Graded Prognostic Assessment will be utilized to evaluate efficacy in this clinical study.
Capecitabine is a prodrug which is enzymatically converted to 5-fluorouracil in its tumor target where it inhibits DNA synthesis and slows tumor growth. It is currently FDA approved for both colorectal and breast cancer. BMK120 is a pan phosphatidylinositol-3-kinase inhibitor being developed under IND# 102,823 by Novartis Corporation. As of September 2012 over 600 patients had been enrolled in fourteen separate Novartis sponsored monotherapy or combination therapy clinical studies of BMK120.
Phosphatidylinositol-3-kinase (PI3K) signaling regulates diverse cellular functions including cell proliferation, survival, translational regulation of protein synthesis, glucose metabolism, cell migration, and angiogenesis. PI3K signaling also serves a central role in the pathogenesis of numerous cancers.
Constitutive activation of PI3K signaling is known to be a critical step in mediating the transforming potential of oncogenes and tumor suppressors in many tumor types. Resistance to a variety of therapeutic interventions, including hormonal therapy, anti-HER2 therapies and chemotherapy can also be linked to constitutive activation of the PI3K pathway.
Preliminary data suggest that activation of the PI3K pathway is a predictor of a poor prognostic outcome in many cancer types. Thus, as a pan-PI3K inhibitor, BMK120 may provide a therapeutic benefit to patients with MBC. Both capecitabine and BMK120 have previously shown activity in patients with MBC. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with MBC.
Trastuzumab is a monoclonal antibody that targets the HER2 receptor which is overexpressed or amplified in approximately 20-25% of breast cancers. The clinical benefit of trastuzumab in women with metastatic breast cancer has been demonstrated in two pivotal studies.
Current clinical experience with BMK120 has shown that its most frequent adverse events (AEs) include fatigue, decreased appetite, diarrhea, hyperglycemia, nausea, rash and mood alteration disorders. Therefore patients will be closely monitored for fasting plasma glucose (FPG) HbA1c, and insulin C-peptide. Patients will also be frequently and routinely evaluated for mood disorders and disturbances. The remaining most frequent AEs will be detected by regular, frequent monitoring with symptomatic treatment to be provided as required.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02000882
|Contact: Zuzanne Bristow, MPHfirstname.lastname@example.org|
|Contact: Karla B Polkemail@example.com|
|United States, Texas|
|Please contact Zuzanne Bristow for list of sites||Recruiting|
|Sites are part of US Onc network, & are added as pts identified, Texas, United States|
|Principal Investigator:||Joyce A. O'Shaughnessy, MD||US Oncology Research, McKesson Specialty Health|
|Principal Investigator:||Morris D. Groves, MD, JD||US Oncology Research, McKesson Specialty Health|