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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.
Scientific title
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
Secondary ID [1] 0 0
CLEE011X2105
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Metastatic BRAF Mutant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
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).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Timepoint [1] 0 0
Cycle 1 (approximately 28 days)
Primary outcome [2] 0 0
Phase II - Progression Free Survival (PFS)
Timepoint [2] 0 0
Approximately 23 months after enrollment
Primary outcome [3] 0 0
Phase II - Objective Response Rate (ORR)
Timepoint [3] 0 0
Approximately 23 months after enrollment
Secondary outcome [1] 0 0
Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
Timepoint [1] 0 0
Approximately 23 months after enrollment
Secondary outcome [2] 0 0
Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
Timepoint [2] 0 0
Approximately 23 months after enrollment
Secondary outcome [3] 0 0
Phase Ib/II - Plasma Concentration-time Profiles
Timepoint [3] 0 0
28-day cycles
Secondary outcome [4] 0 0
Phase Ib/II - Overall Response Rate (ORR)
Timepoint [4] 0 0
Approximately 23 months after enrollment
Secondary outcome [5] 0 0
Phase Ib/II - Progression Free Survival (PFS)
Timepoint [5] 0 0
Approximately 23 months after enrollment
Secondary outcome [6] 0 0
Phase Ib/II - Duration Of Response (DOR)
Timepoint [6] 0 0
Approximately 23 months after enrollment
Secondary outcome [7] 0 0
Phase II - Overall Survival (OS)
Timepoint [7] 0 0
Approximately 23 months after enrollment
Secondary outcome [8] 0 0
Phase Ib/II - Pharmacokinetic Parameters: AUCtau
Timepoint [8] 0 0
28-day cycles
Secondary outcome [9] 0 0
Phase Ib/II - Pharmacokinetic Parameters: Cmin
Timepoint [9] 0 0
28-day cycles
Secondary outcome [10] 0 0
Phase Ib/II - Pharmacokinetic Parameters: Cmax
Timepoint [10] 0 0
28-day cycles
Secondary outcome [11] 0 0
Phase Ib/II - Pharmacokinetic Parameters: Tmax
Timepoint [11] 0 0
28-day cycles
Secondary outcome [12] 0 0
Phase Ib/II - Pharmacokinetic Parameters: Racc
Timepoint [12] 0 0
28-day cycles

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2015
Sample size
Target
Accrual to date
Final
28
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Westmead
Recruitment hospital [2] 0 0
Novartis Investigative Site - Woodville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
Netherlands
State/province [7] 0 0
Utrecht

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Array BioPharma
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered orally to patients with BRAF mutant melanoma.
Trial website
https://clinicaltrials.gov/study/NCT01777776
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Array BioPharma
Address 0 0
303-381-6604
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01777776