Dose EscalationPhase 1NCT01576666
Phase Ib, Dose Escalation Study of Oral LDE225 in Combination With BKM120 in Patients With Advanced Solid Tumors
A Phase 1 study testing LDE225 and BKM120 in people with Dose Escalation and Safety, run by Novartis Pharmaceuticals at 23 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dose Escalation, Safety, Preliminary Efficacy
- What is being tested?
- LDE225 and BKM120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 23 sitesin 8 countries
- Study dates
- Jul 2012to Apr 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Patient is able to swallow and retain oral medication
- Negative serum pregnancy test; non-lactating or post-menopausal women.
- 3. Provision of an archival tumor sample to a Novartis designated laboratory for molecular profiling. It is accepted that it may not be possible to obtain all samples prior to commencing study treatment. It is also accepted that it may not be possible to obtain a sample (e.g. if sufficient sample does not exist), and in this situation inclusion of the patient should be discussed with Novartis (as this may not make a patient ineligible).
Who cannot join
- 1.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.
- 3.Patient has received previous treatment with PI3K inhibitors and/or smoothened inhibitors.
- 4.Patients with recurrent GBM who have received radiotherapy within 3 months of initiating study treatment.
- 5.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.
- 6.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.
- 7.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.
Show all 31Show fewer
- 8.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.
- 9.Patient has a score ≥12 on the PHQ-9 questionnaire. A normal evaluation by a psychiatrist or psychologist can overrule this exclusion).
- 10.Patients who select responses of "1", "2" or "3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9), (a normal evaluation by a psychiatrist or psychologist can overrule this exclusion).
- 11.Patient has a GAD-7 mood scale score ≥ 15, (a normal evaluation by a psychiatrist or psychologist can overrule this exclusion) 12.Patient has a documented medical history of or active major depression episode, bipolar disorder (I or II), obsessive compulsive disorder, schizophrenia, a history of suicidal attempts or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) 13. Patient has ≥CTCAE grade 3 anxiety 14.Current medical history of the following:
- 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.
- 21.Patients is currently receiving increasing or chronic treatment with corticosteroids ((≥ the anti-inflammatory potency of 4mg dexamethasone) or another immunosuppressive agent.
- 22.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)
- AMENDMENT 1 CHANGES:
- 5. 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 eligible. The patient must have completed any prior treatment for CNS metastases (including radiotherapy and/or surgery) ≥ 28 days (> 14 days for stereotactic radiosurgery).
- 9. Patient has a score ≥12 on the PHQ-9 questionnaire. A normal evaluation by a psychiatrist can overrule this exclusion.
- 10.Patients who select responses of "1", "2" or "3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9), (a normal evaluation by a psychiatrist can overrule this exclusion).
- 11.Patient has a GAD-7 mood scale score ≥ 15, (a normal evaluation by a psychiatrist can overrule this exclusion)
- AMENDMENT 2 CHANGES:
- Updated Inclusion Criteria:
- 3. Revised to specify the groups of patients that will be included in the dose escalation and dose expansion parts (NEW tumor type added here): Patients with histologically/cytologically confirmed diagnosis of the following advanced tumors that have progressed despite standard therapy or that have no available established treatments: four group of patients during the dose escalation part: metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic CRC or recurrent GBM and five groups during the dose expansion part: triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, recurrent GBM, GASTRIC/GASTROESOPHAGEAL JUNCTION CANCER, advanced pancreatic adenocarcinoma or metastatic CRC will be included.
- 6. ECOG (WHO) performance status 0-2. ADDED "only applies to patients enrolled under the original and Amendment 1 protocol versions." 7. Two sub-bullets updated: Potassium, and calcium, within normal limits for the institution. Out of range values should be clinically insignificant. Serum Creatinine ≤ 1.5 x ULN and 24-hour creatinine clearance ≥ 50 mL/min (determined by inputting the serum creatinine result into the Cockcroft-Gault formula).
- 9. NEW Inclusion criterion: Recurrent GBM patient has a Karnofsky performance status (KPS) score ≥ 70.
- 10. NEW Inclusion criterion:ECOG (WHO) performance status 0-1 (only applies to patients enrolled under Amendment 2 and any later protocol versions).
- Updated Exclusion Criteria:
- 12. Patient has a score ≥12 on the PHQ-9 questionnaire. REMOVED "A normal evaluation by a psychiatrist can overrule this exclusion." 13.Patients who select responses of "1", "2" or "3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9). REMOVED "A normal evaluation by a psychiatrist can overrule this exclusion." 14. Patient has a GAD-7 mood scale score ≥ 15. REMOVED "A normal evaluation by a psychiatrist can overrule this exclusion." 15. Patient has a documented medical history of or active major depression episode, bipolar disorder (I or II), obsessive compulsive disorder, schizophrenia, a history of suicidal attempts or ideation. ADDED "or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM- IV, Diagnostic and Statistical Manual of Mental Disorders, 4th edition) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug." 23. REMOVED mention of "Double barrier method" term under "Male patient" section 27. Patient who has received chemotherapy, targeted therapy or immunotherapy ≤ 3 weeks (6 weeks for nitrosourea, or mitomycin-C; or 6 weeks for monoclonal antibodies if carryover effects are suspected; 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). ADDED clarification concerning the washout period for monoclonal antibodies.
Trial locations and contacts
23 sites in 8 countries.
23 sites in 8 countries
United States13 sites
Dana Farber Cancer Institute Dana SC
Boston, Massachusetts, 02215
Texas Oncology Midtown Texas Oncology
Dallas, Texas, 75251
Sammons Cancer Center - Texas Oncology SC-2
Dallas, Texas, 78246
Duke University Medical Center Duke - Baker
Durham, North Carolina, 27710
Willamette Valley Clinical Studies Williamette Valley Cancer
Eugene, Oregon, 97404
University of Texas/MD Anderson Cancer Center SC-3
Houston, Texas, 77030-4009
Cedars Sinai Medical Center SC
Los Angeles, California, 90048
Fox Chase Cancer Center FCCC
Philadelphia, Pennsylvania, 19111-2497
Northwest Cancer Specialists Northwest Cancer
Portland, Oregon, 97210
Mayo Clinic - Rochester Division of Hematology
Rochester, Minnesota, 55905
University of Utah / Huntsman Cancer Institute Huntsman
Salt Lake City, Utah, 84103
University of California San Francisco UCSF (SC)
San Francisco, California, 94101
H. Lee Moffitt Cancer Center & Research Institute Moffitt 4
Tampa, Florida, 33612
Italy2 sites
Novartis Investigative Site
Ancona, AN, 60126
Novartis Investigative Site
Milan, MI, 20133
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08035
United Kingdom2 sites
Novartis Investigative Site
Glasgow, G12 0YN
Novartis Investigative Site
Sutton, SM2 5PT
About this study
Official title: A Phase Ib, Multi-center, Open Label, Dose Escalation Study of Oral LDE225 in Combination With BKM 120 in Patients With Advanced Solid Tumors
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).
Read the detailed description
The primary purpose of this study is to determine a combination maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LDE225 and BKM120 when co-administered orally in patients with advanced solid tumors. Adult patients, aged > 18 years with advanced solid tumors that have progressed despite standard therapy or for which no standard therapies exist will be eligible for this study.
In the dose escalation part of the study, four groups of patients with the following tumor types will be enrolled: recurrent GBM, metastatic breast cancer, metastatic CRC and advanced pancreatic adenocarcinoma. It is anticipated that approximately 45 patients will be enrolled in the dose escalation part. Approximately 15 GBM patients (maximum of 2 patients per dose level) will be enrolled to previously well-tolerated doses during dose escalation if no slot is available in a cohort under active testing. In the dose expansion part of the study, five groups of patients (approximately 15 patients per group) with the following tumor types will be enrolled: recurrent GBM, triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, gastric/gastroesophageal junction cancer, and a combined maximum of 15 patients with metastatic CRC or advanced pancreatic adenocarcinoma. The dose expansion will enroll approximately 75 patients. Accounting for patients who may withdraw or who may not meet the eligibility criteria, it is expected that this study will enroll approximately 120 patients.
This is a multi-center, open-label, dose finding, phase Ib study to determine the MTD and/or RDE for the combination of LDE225 plus BKM120, followed by an expansion part to further assess safety and preliminary efficacy of the combination in patients with advanced solid tumors that are frequently associated with dysregulated Hh and/or PI3K pathways, specifically triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic CRC, recurrent GBM and gastric/gastroesophageal junction cancer patients. Patients will be treated daily on 28-day cycles. Dose escalation will be dependent on the available toxicity information (including adverse events that are not DLTs), PK, PD, and efficacy information, as well as the recommendations from the Bayesian Logistic Regression Model (BLRM).
- Conditions
- Dose Escalation, Safety, Preliminary Efficacy, Advanced Solid Tumors, Metastatic Breast Cancer, Advanced Pancreatic Adenocarcinoma
- Being tested
- LDE225, BKM120
- Keywords
- Dose escalation, Maximum Tolerated Dose, MTD, Safety Expansion, Safety, Preliminary Efficacy, Objective Response Rate, Early progression rate, PI3K activation, Combination Treatment, Hedgehog Signaling Pathway, Smoothened inhibitor, Phosphoinositide-3' kinase, Phosphatase signaling pathway, Advanced solid tumors, metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic colorectal cancer, recurrent glioblastoma multiforme, gastric cancer
- Medical subject headings
- Breast Neoplasms, Colorectal Neoplasms, Glioblastoma, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LDE225Drug
BKM120Drug
| Study group | Role | What they receive |
|---|---|---|
| LDE225 and BKM120 in combination | Experimental | LDE225 and BKM120 in combination Receives: Drug: LDE225; Drug: BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities
Dose Limiting Toxicities (DLTs) during the first 6 weeks (42 days) of the combination treatment of LDE225 and BKM120.
Measured: 6 weeks (42 days)
Secondary outcomes (4)
Number of Patients with Adverse Events and Serious Adverse Events
Adverse and serious adverse events, changes in hematology and chemistry values, and assessment of physical and/or neurological examinations, vital signs, and electrocardiograms
Measured: Following signing of the informed consent form, up to and including 30 days following the last dose
Objective response rate (ORR)
ORR is the proportion of patients with best overall response of complete or partial response. ORR will be used to evaluate preliminary efficacy of the combination therapy. Tumors will be assessed using Investigator read CT/MRI assessments evaluated as per RECIST 1.1, except for patients with glioblastoma multiforme (GBM) who will be assessed per the RANO Criteria.
Measured: 4 months
Early progression rate (EPR)
EPR is the proportion of patients with progressive disease within 6 months of the start of treatment. EPR will be used to evaluate preliminary efficacy of the combination therapy. Tumors will be assessed using Investigator read CT/MRI assessments evaluated as per RECIST 1.1, except for patients with GBM who will be assessed per the RANO Criteria. AMENDMENT #2 change: EPR duration modified to 6 months for recurrent GBM patients per the convention for that tumor type
Measured: 6 months
Plasma pharmacokinetics (PK) parameters
Plasma PK parameters of LDE225 and plasma PK parameters of BKM120.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startJul 2012
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Dose EscalationStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmceuticals, Study director, Novartis Pharmceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576666
- Sponsor's protocol ID
- CLDE225X2114
- Other IDs
- 2011-005016-28
- Status last verified
- Feb 2016
- First submitted
- 10 Apr 2012
- Last updated
- 19 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib, Multi-center, Open Label, Dose Escalation Study of Oral LDE225 in Combination With BKM 120 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT01576666
- Acronym / sponsor ID
- CLDE225X2114
- Conditions
- Dose Escalation, Safety, Preliminary Efficacy, Advanced Solid Tumors, Metastatic Breast Cancer, Advanced Pancreatic Adenocarcinoma
- Keywords
- Dose escalation, Maximum Tolerated Dose, MTD, Safety Expansion, Safety, Preliminary Efficacy, Objective Response Rate, Early progression rate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 12 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The primary purpose of this study is to determine a combination maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of LDE225 and BKM120 when co-administered orally in patients with advanced solid tumors. Adult patients, aged > 18 years with advanced solid tumors that have progressed despite standard therapy or for which no standard therapies exist will be eligible for this study.
In the dose escalation part of the study, four groups of patients with the following tumor types will be enrolled: recurrent GBM, metastatic breast cancer, metastatic CRC and advanced pancreatic adenocarcinoma. It is anticipated that approximately 45 patients will be enrolled in the dose escalation part. Approximately 15 GBM patients (maximum of 2 patients per dose level) will be enrolled to previously well-tolerated doses during dose escalation if no slot is available in a cohort under active testing. In the dose expansion part of the study, five groups of patients (approximately 15 patients per group) with the following tumor types will be enrolled: recurrent GBM, triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, gastric/gastroesophageal junction cancer, and a combined maximum of 15 patients with metastatic CRC or advanced pancreatic adenocarcinoma. The dose expansion will enroll approximately 75 patients. Accounting for patients who may withdraw or who may not meet the eligibility criteria, it is expected that this study will enroll approximately 120 patients.
This is a multi-center, open-label, dose finding, phase Ib study to determine the MTD and/or RDE for the combination of LDE225 plus BKM120, followed by an expansion part to further assess safety and preliminary efficacy of the combination in patients with advanced solid tumors that are frequently associated with dysregulated Hh and/or PI3K pathways, specifically triple negative metastatic breast cancer, hormone receptor positive (ER+/PR+, and Her2-) metastatic breast cancer, advanced pancreatic adenocarcinoma, metastatic CRC, recurrent GBM and gastric/gastroesophageal junction cancer patients. Patients will be treated daily on 28-day cycles. Dose escalation will be dependent on the available toxicity information (including adverse events that are not DLTs), PK, PD, and efficacy information, as well as the recommendations from the Bayesian Logistic Regression Model (BLRM).
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LDE225 and BKM120 in combination | Experimental | Drug: LDE225, Drug: BKM120LDE225 and BKM120 in combination |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (31 listed)
- 1.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.
- 3.Patient has received previous treatment with PI3K inhibitors and/or smoothened inhibitors.
- 4.Patients with recurrent GBM who have received radiotherapy within 3 months of initiating study treatment.
- 5.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.
- 6.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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LDE225 | Drug | LDE225 and BKM120 in combination |
| BKM120 | Drug | LDE225 and BKM120 in combination |
Primary outcome
Dose Limiting Toxicities
Time frame: 6 weeks (42 days)
Dose Limiting Toxicities (DLTs) during the first 6 weeks (42 days) of the combination treatment of LDE225 and BKM120.
4 secondary outcomes
Number of Patients with Adverse Events and Serious Adverse Events
Time frame: Following signing of the informed consent form, up to and including 30 days following the last dose
Objective response rate (ORR)
Time frame: 4 months
Early progression rate (EPR)
Time frame: 6 months
Plasma pharmacokinetics (PK) parameters
Time frame: 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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2020.
- Results for CLDE225X2114 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmceuticals study director
Novartis Pharmceuticals
23 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LDE225 and BKM120 in people with Dose Escalation and Safety, run by Novartis Pharmaceuticals at 23 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, Italy, Spain, United Kingdom, Australia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities (time frame: 6 weeks (42 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2020.