- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01777776
Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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New South Wales
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Westmead, New South Wales, Australia, 2145
- Novartis Investigative Site
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South Australia
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Woodville, South Australia, Australia, 5011
- Novartis Investigative Site
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Quebec
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Montreal, Quebec, Canada, H2X 3J4
- Novartis Investigative Site
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Utrecht, Netherlands, 3584CX
- Novartis Investigative Site
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Colorado
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Aurora, Colorado, United States, 80045
- University of Colorado Dept of Oncology
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Michigan
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Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute Dept of Oncology
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New York
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NY, New York, United States, 90033
- Memorial Sloan Kettering Cancer Center Dept Oncology
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health & Science University Dept. of OHSU (3)
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Tennessee
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Nashville, Tennessee, United States, 37232
- Vanderbilt University Medical Center SC - Dept of Oncology .
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age ≥18 years.
- Diagnosis of locally advanced or metastatic melanoma along with written documentation of BRAF V600 mutation.
- ECOG performance status of 0 - 2.
- Patients enrolled into Phase Ib must have evidence of evaluable and/or measurable disease as determined by RECIST v1.1.
- Patients enrolled into Phase II (BRAFi naïve and resistant) must have evidence of measurable disease as determined by RECIST v1.1.
- Archival tumor tissue must be obtained for patients enrolled in Phase Ib and Phase II arm 1a/b- BRAFi naïve patients. If an archival tumor tissue is not available, a fresh tumor sample is acceptable.
- For patients enrolled in the phase II arm 2, patients must agree to undergo a fresh tumor biopsy unless one was collected prior to study entry but at the time of disease relapse from the most recent BRAFi treatment.
Exclusion Criteria:
- Symptomatic brain metastases.
- Symptomatic or untreated leptomeningeal disease.
- Patients with inadequate laboratory values during screening.
- In the phase II BRAFi naïve arms (1a/b), prior exposure to CDK4/6 inhibitor (e.g., PD 0332991)
- Impaired cardiac function or clinically significant cardiac diseases.
- Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of LEE011 or LGX818.
- Patients with concurrent severe and/or uncontrolled concurrent medical conditions.
- Previous or concurrent malignancy.
- Major surgery < 2 weeks before starting study treatment
- Known diagnosis of human immunodeficiency virus (HIV) or hepatitis C.
Other protocol-defined inclusion/exclusion criteria may apply.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Phase Ib
Phase Ib will randomize 18 patients with BRAF mutant melanoma, who are naïve or who have progressed on prior therapy to evaluate the safety and tolerability of the combination of LEE011 and LGX818.
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LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
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Experimental: Phase II arm 1a
Phase II arm 1a will randomize 60 patients that are naïve to prior BRAF inhibitor therapy to LGX818+LEE011 to evaluate the effect of adding LEE011 to a BRAFi in this population.
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LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
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Experimental: Phase II arm 1b
Phase II arm 1b will randomize 30 patients to LGX818.
Single agent anti-tumor activity of LGX818 is comparable to other BRAFi that are either approved or in clinical trials.
This single agent anti-tumor activity will be compared to that of the combination (LEE011 + LGX818) in the BRAFi naïve patient population.
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LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
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Experimental: Phase II arm 2
Phase II arm 2 will evaluate a single arm LEE011+LGX818 in 40 patients resistant to prior BRAF inhibitor therapy.
Single agent LGX818 has shown limited activity in patients with melanoma who have failed prior BRAF inhibitor treatment; the contribution of LEE011 in this combination will be evaluated.
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LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Other Names:
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Time Frame: Cycle 1 (approximately 28 days)
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Dose Limiting Toxicities (DLTs) during the first 28 days of the combination treatment of LEE011 and LGX818. Due to the halt of enrollment, no Maximum Tolerated Dose (MTD) was formally declared during the study. |
Cycle 1 (approximately 28 days)
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Phase II - Progression Free Survival (PFS)
Time Frame: Approximately 23 months after enrollment
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As per RECIST v1.1, PFS is the time from date of randomization/ start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed. |
Approximately 23 months after enrollment
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Phase II - Objective Response Rate (ORR)
Time Frame: Approximately 23 months after enrollment
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As per RECIST v1.1, ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to efficacy were not performed. |
Approximately 23 months after enrollment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
Time Frame: Approximately 23 months after enrollment
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Approximately 23 months after enrollment
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Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
Time Frame: Approximately 23 months after enrollment
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Approximately 23 months after enrollment
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Phase Ib/II - Plasma Concentration-time Profiles
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to plasma concentration time profiles were not performed.
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28-day cycles
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Phase Ib/II - Overall Response Rate (ORR)
Time Frame: Approximately 23 months after enrollment
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ORR is defined as the proportion of patients with a best overall response of complete response or partial response. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
Approximately 23 months after enrollment
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Phase Ib/II - Progression Free Survival (PFS)
Time Frame: Approximately 23 months after enrollment
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PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
Approximately 23 months after enrollment
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Phase Ib/II - Duration Of Response (DOR)
Time Frame: Approximately 23 months after enrollment
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DOR is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
Approximately 23 months after enrollment
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Phase II - Overall Survival (OS)
Time Frame: Approximately 23 months after enrollment
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OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive. Due to the halt of enrollment during the Phase Ib part of the study, this analysis was not performed. |
Approximately 23 months after enrollment
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Phase Ib/II - Pharmacokinetic Parameters: AUCtau
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
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28-day cycles
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Phase Ib/II - Pharmacokinetic Parameters: Cmin
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
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28-day cycles
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Phase Ib/II - Pharmacokinetic Parameters: Cmax
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
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28-day cycles
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Phase Ib/II - Pharmacokinetic Parameters: Tmax
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
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28-day cycles
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Phase Ib/II - Pharmacokinetic Parameters: Racc
Time Frame: 28-day cycles
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Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
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28-day cycles
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLEE011X2105
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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