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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01777776
Registration number
NCT01777776
Ethics application status
Date submitted
22/01/2013
Date registered
29/01/2013
Date last updated
13/09/2016
Titles & IDs
Public title
Safety and Efficacy of LEE011 and LGX818 in Patients With BRAF Mutant Melanoma.
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Scientific title
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
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Secondary ID [1]
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CLEE011X2105
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Metastatic BRAF Mutant Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LEE011
Treatment: Drugs - LGX818
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.
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.
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.
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.
Treatment: Drugs: LEE011
LEE011 will be administered orally, once daily for 21 consecutive days followed by a 7-day planned break (28-day cycle).
Treatment: Drugs: LGX818
LGX818 will be administered orally, once daily on a continuous dosing schedule (28-day cycle).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
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Assessment method [1]
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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.
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Timepoint [1]
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Cycle 1 (approximately 28 days)
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Primary outcome [2]
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Phase II - Progression Free Survival (PFS)
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Assessment method [2]
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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.
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Timepoint [2]
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Approximately 23 months after enrollment
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Primary outcome [3]
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Phase II - Objective Response Rate (ORR)
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Assessment method [3]
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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.
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Timepoint [3]
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Approximately 23 months after enrollment
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Secondary outcome [1]
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Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
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Assessment method [1]
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Timepoint [1]
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Approximately 23 months after enrollment
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Secondary outcome [2]
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Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
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Assessment method [2]
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Timepoint [2]
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Approximately 23 months after enrollment
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Secondary outcome [3]
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Phase Ib/II - Plasma Concentration-time Profiles
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Assessment method [3]
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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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Timepoint [3]
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28-day cycles
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Secondary outcome [4]
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Phase Ib/II - Overall Response Rate (ORR)
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Assessment method [4]
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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.
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Timepoint [4]
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Approximately 23 months after enrollment
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Secondary outcome [5]
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Phase Ib/II - Progression Free Survival (PFS)
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Assessment method [5]
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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.
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Timepoint [5]
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Approximately 23 months after enrollment
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Secondary outcome [6]
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Phase Ib/II - Duration Of Response (DOR)
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Assessment method [6]
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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.
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Timepoint [6]
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Approximately 23 months after enrollment
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Secondary outcome [7]
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Phase II - Overall Survival (OS)
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Assessment method [7]
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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.
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Timepoint [7]
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Approximately 23 months after enrollment
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Secondary outcome [8]
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Phase Ib/II - Pharmacokinetic Parameters: AUCtau
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Assessment method [8]
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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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Timepoint [8]
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28-day cycles
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Secondary outcome [9]
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Phase Ib/II - Pharmacokinetic Parameters: Cmin
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Assessment method [9]
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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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Timepoint [9]
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28-day cycles
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Secondary outcome [10]
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Phase Ib/II - Pharmacokinetic Parameters: Cmax
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Assessment method [10]
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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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Timepoint [10]
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28-day cycles
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Secondary outcome [11]
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Phase Ib/II - Pharmacokinetic Parameters: Tmax
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Assessment method [11]
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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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Timepoint [11]
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28-day cycles
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Secondary outcome [12]
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Phase Ib/II - Pharmacokinetic Parameters: Racc
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Assessment method [12]
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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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Timepoint [12]
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28-day cycles
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Eligibility
Key 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Stopped early
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/07/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/04/2015
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Sample size
Target
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Accrual to date
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Final
28
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Recruitment in Australia
Recruitment state(s)
NSW,SA
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Recruitment hospital [1]
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Novartis Investigative Site - Westmead
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Recruitment hospital [2]
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Novartis Investigative Site - Woodville
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Recruitment postcode(s) [1]
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2145 - Westmead
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Recruitment postcode(s) [2]
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5011 - Woodville
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Colorado
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Country [2]
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United States of America
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State/province [2]
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Michigan
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Country [3]
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United States of America
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State/province [3]
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New York
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Country [4]
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United States of America
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State/province [4]
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Oregon
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Country [5]
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United States of America
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State/province [5]
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Tennessee
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Country [6]
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Canada
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State/province [6]
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Quebec
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Country [7]
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Netherlands
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State/province [7]
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Utrecht
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Array BioPharma
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.
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Trial website
https://clinicaltrials.gov/study/NCT01777776
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Array BioPharma
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Address
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303-381-6604
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01777776
Download to PDF