Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors
A Phase Ib, Multi-center, Open Label, Dose Escalation Study of Oral LDE225 in Combination With BKM 120 in Patients With Advanced Solid Tumors
2 other identifiers
interventional
120
8 countries
23
Brief Summary
The purpose of this study is to determine the maximum dose of LDE225 and BKM120 that can be safely given together to patients and/or the dose that will be used in future studies. This study will also learn more about how the combination of these two investigational drugs may work for patients with certain cancers (specifically metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic colorectal cancer and recurrent glioblastoma multiforme).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2012
Typical duration for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2012
CompletedFirst Posted
Study publicly available on registry
April 12, 2012
CompletedStudy Start
First participant enrolled
July 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2015
CompletedDecember 19, 2020
February 1, 2016
2.8 years
April 10, 2012
December 16, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Dose Limiting Toxicities
Dose Limiting Toxicities (DLTs) during the first 6 weeks (42 days) of the combination treatment of LDE225 and BKM120.
6 weeks (42 days)
Secondary Outcomes (4)
Number of Patients with Adverse Events and Serious Adverse Events
Following signing of the informed consent form, up to and including 30 days following the last dose
Objective response rate (ORR)
4 months
Early progression rate (EPR)
6 months
Plasma pharmacokinetics (PK) parameters
In 28-day cycles: Cycle 1/Day 1 and Day 15; Cycle 2/Day 1 and Day 15; then on Day 1 of each additional cycle up to and including cycle 11 (if applicable)
Study Arms (1)
LDE225 and BKM120 in combination
EXPERIMENTALLDE225 and BKM120 in combination
Interventions
Eligibility Criteria
You may qualify if:
- Male or female adult patients (\> 18 years)
- Patients with histologically/cytologically confirmed diagnosis of the following advanced tumors that have progressed despite standard therapy or that have no available established treatments: metastatic breast cancer, pancreatic adenocarcinoma, metastatic CRC or recurrent GBM will be included.
- Provision of an archival tumor sample to a Novartis designated laboratory for molecular profiling. The tumor material submitted for these analyses may have been obtained at any time during the course of the patient's disease.
- Measurable disease as assessed by RECIST 1.1 for non-GBM tumors and by RANO criteria for GBM.
- ECOG (WHO) performance status 0-2
- Adequate bone marrow and organ function
- Patient is able to swallow and retain oral medication
- Negative serum pregnancy test; non-lactating or post-menopausal women.
You may not qualify if:
- Use of other investigational drugs within 30 days of enrollment or 5 half-lives of enrollment, whichever is longer. 2.History of hypersensitivity to LDE225, BKM120 or to drugs of similar chemical classes.
- Patient has received previous treatment with PI3K inhibitors and/or smoothened inhibitors.
- Patients with recurrent GBM who have received radiotherapy within 3 months of initiating study treatment.
- Patients with primary CNS tumor (except recurrent GBM), uncontrolled or symptomatic CNS metastasis. However, patients with controlled, asymptomatic or with resected CNS metastases with no radiological evidence of disease or with stable brain metastasis with no progression may be are eligible.
- Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis, such as HMG CoA inhibitors (statins), clofibrate and gemfibrozil. If it is essential that the patient remains on a statin to control hyperlipidemia, only Pravastatin may be used with extra caution.
- Patients who require the use of warfarin (substrate of CYP2C9) cannot be enrolled as LDE225 and BKM120 are competitive inhibitors of CYP2C9 based on in-vitro data.
- Patient is currently being treated with drugs known to be strong inhibitors or inducers of CYP3A4/5, which cannot be discontinued or switched to a different medication 7 days prior to starting study treatment and for the duration of the study.
- Use of a pacemaker
- History of or presence of clinically significant ventricular or atrial tachyarrhythmia
- Clinically significant resting bradycardia (\< 45 beats per minute)
- History of clinically documented myocardial infarction
- History of unstable angina pectoris
- History of known structural abnormalities (i.e. cardiomyopathy) 15.Clinically significant cardio-vascular disease 16.Clinically significant abnormal ECG 17.Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated Acquisition (MUGA) scan or echocardiogram (ECHO) 18.Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication 7 days prior to starting the study and for the duration of the study 19.Patients who are not willing to apply highly effective contraception as defined by the protocol during the study and through the duration of the study. Note: Hormonal contraception methods (e.g. oral, injected, implanted) are not allowed as it cannot be ruled out that the study drug decreases the effectiveness of hormonal contraception 20.Sexually active males who are unwilling to use a condom during intercourse while taking drug and for 6 months after stopping investigational medications and agree not father a child in this period.
- Patients is currently receiving increasing or chronic treatment with corticosteroids ((≥ the anti-inflammatory potency of 4mg dexamethasone) or another immunosuppressive agent.
- Patient has been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued 23.Patient who has received chemotherapy, targeted therapy or immunotherapy ≤ 3 weeks (6 weeks for nitrosourea, mitomycin-C or monoclonal antibodies; 1 week for hormonal anti-cancer therapy) prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia, bone marrow and organ functions) 24.Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of LDE225 and BKM120 (e.g., ulcerative colitis, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) 25.Patient has a known history of HIV infection (testing not mandatory)
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Cedars Sinai Medical Center SC
Los Angeles, California, 90048, United States
University of California San Francisco UCSF (SC)
San Francisco, California, 94101, United States
H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
Tampa, Florida, 33612, United States
Dana Farber Cancer Institute Dana SC
Boston, Massachusetts, 02215, United States
Mayo Clinic - Rochester Division of Hematology
Rochester, Minnesota, 55905, United States
Duke University Medical Center Duke - Baker
Durham, North Carolina, 27710, United States
Willamette Valley Clinical Studies Williamette Valley Cancer
Eugene, Oregon, 97404, United States
Northwest Cancer Specialists Northwest Cancer
Portland, Oregon, 97210, United States
Fox Chase Cancer Center FCCC
Philadelphia, Pennsylvania, 19111-2497, United States
Texas Oncology Midtown Texas Oncology
Dallas, Texas, 75251, United States
Sammons Cancer Center - Texas Oncology SC-2
Dallas, Texas, 78246, United States
University of Texas/MD Anderson Cancer Center SC-3
Houston, Texas, 77030-4009, United States
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, 84103, United States
Novartis Investigative Site
Parkville, Victoria, 3050, Australia
Novartis Investigative Site
Wilrijk, 2610, Belgium
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2, Canada
Novartis Investigative Site
Essen, 45147, Germany
Novartis Investigative Site
Ancona, AN, 60126, Italy
Novartis Investigative Site
Milan, MI, 20133, Italy
Novartis Investigative Site
Barcelona, Catalonia, 08003, Spain
Novartis Investigative Site
Barcelona, Catalonia, 08035, Spain
Novartis Investigative Site
Glasgow, G12 0YN, United Kingdom
Novartis Investigative Site
Sutton, SM2 5PT, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Novartis Pharmceuticals
Novartis Pharmceuticals
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2012
First Posted
April 12, 2012
Study Start
July 1, 2012
Primary Completion
April 1, 2015
Study Completion
April 1, 2015
Last Updated
December 19, 2020
Record last verified: 2016-02