Please note that the copy function is not enabled for this field.
If you wish to
modify
existing outcomes, please copy and paste the current outcome text into the Update field.
LOGIN
CREATE ACCOUNT
LOGIN
CREATE ACCOUNT
MY TRIALS
REGISTER TRIAL
FAQs
HINTS AND TIPS
DEFINITIONS
Trial Review
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this
information for consumers
Download to PDF
Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/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.
Query!
Scientific title
A Phase Ib/II, Multicenter, Study of LEE011 in Combination With LGX818 in Adult Patients With BRAF Mutant Melanoma.
Query!
Secondary ID [1]
0
0
CLEE011X2105
Query!
Universal Trial Number (UTN)
Query!
Trial acronym
Query!
Linked study record
Query!
Health condition
Health condition(s) or problem(s) studied:
Locally Advanced Metastatic BRAF Mutant Melanoma
0
0
Query!
Condition category
Condition code
Cancer
0
0
0
0
Query!
Malignant melanoma
Query!
Intervention/exposure
Study type
Interventional
Query!
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).
Query!
Intervention code [1]
0
0
Treatment: Drugs
Query!
Comparator / control treatment
Query!
Control group
Query!
Outcomes
Primary outcome [1]
0
0
Phase Ib - Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
Query!
Assessment method [1]
0
0
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.
Query!
Timepoint [1]
0
0
Cycle 1 (approximately 28 days)
Query!
Primary outcome [2]
0
0
Phase II - Progression Free Survival (PFS)
Query!
Assessment method [2]
0
0
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.
Query!
Timepoint [2]
0
0
Approximately 23 months after enrollment
Query!
Primary outcome [3]
0
0
Phase II - Objective Response Rate (ORR)
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [1]
0
0
Phase I - Number of Subjects Experiencing at Least One Adverse Event (AE).
Query!
Assessment method [1]
0
0
Query!
Timepoint [1]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [2]
0
0
Phase I - Number of Subjects Experiencing at Least One Serious Adverse Event (SAE).
Query!
Assessment method [2]
0
0
Query!
Timepoint [2]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [3]
0
0
Phase Ib/II - Plasma Concentration-time Profiles
Query!
Assessment method [3]
0
0
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.
Query!
Timepoint [3]
0
0
28-day cycles
Query!
Secondary outcome [4]
0
0
Phase Ib/II - Overall Response Rate (ORR)
Query!
Assessment method [4]
0
0
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.
Query!
Timepoint [4]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [5]
0
0
Phase Ib/II - Progression Free Survival (PFS)
Query!
Assessment method [5]
0
0
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.
Query!
Timepoint [5]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [6]
0
0
Phase Ib/II - Duration Of Response (DOR)
Query!
Assessment method [6]
0
0
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.
Query!
Timepoint [6]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [7]
0
0
Phase II - Overall Survival (OS)
Query!
Assessment method [7]
0
0
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.
Query!
Timepoint [7]
0
0
Approximately 23 months after enrollment
Query!
Secondary outcome [8]
0
0
Phase Ib/II - Pharmacokinetic Parameters: AUCtau
Query!
Assessment method [8]
0
0
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Query!
Timepoint [8]
0
0
28-day cycles
Query!
Secondary outcome [9]
0
0
Phase Ib/II - Pharmacokinetic Parameters: Cmin
Query!
Assessment method [9]
0
0
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Query!
Timepoint [9]
0
0
28-day cycles
Query!
Secondary outcome [10]
0
0
Phase Ib/II - Pharmacokinetic Parameters: Cmax
Query!
Assessment method [10]
0
0
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Query!
Timepoint [10]
0
0
28-day cycles
Query!
Secondary outcome [11]
0
0
Phase Ib/II - Pharmacokinetic Parameters: Tmax
Query!
Assessment method [11]
0
0
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Query!
Timepoint [11]
0
0
28-day cycles
Query!
Secondary outcome [12]
0
0
Phase Ib/II - Pharmacokinetic Parameters: Racc
Query!
Assessment method [12]
0
0
Due to the halt of enrollment during the Phase Ib part of the study, all analyses related to pharmacokinetic parameters were not performed.
Query!
Timepoint [12]
0
0
28-day cycles
Query!
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.
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
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.
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1/Phase 2
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Terminated
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/07/2013
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/04/2015
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
28
Query!
Recruitment in Australia
Recruitment state(s)
NSW,SA
Query!
Recruitment hospital [1]
0
0
Novartis Investigative Site - Westmead
Query!
Recruitment hospital [2]
0
0
Novartis Investigative Site - Woodville
Query!
Recruitment postcode(s) [1]
0
0
2145 - Westmead
Query!
Recruitment postcode(s) [2]
0
0
5011 - Woodville
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Colorado
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Michigan
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
New York
Query!
Country [4]
0
0
United States of America
Query!
State/province [4]
0
0
Oregon
Query!
Country [5]
0
0
United States of America
Query!
State/province [5]
0
0
Tennessee
Query!
Country [6]
0
0
Canada
Query!
State/province [6]
0
0
Quebec
Query!
Country [7]
0
0
Netherlands
Query!
State/province [7]
0
0
Utrecht
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Query!
Name
Array BioPharma
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
To evaluate the safety, tolerability and efficacy of LEE011 and LGX818 when administered
orally to patients with BRAF mutant melanoma.
Query!
Trial website
https://clinicaltrials.gov/ct2/show/NCT01777776
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Array BioPharma
Query!
Address
0
0
303-381-6604
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01777776
Download to PDF