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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01543698




Registration number
NCT01543698
Ethics application status
Date submitted
1/02/2012
Date registered
5/03/2012
Date last updated
21/04/2020

Titles & IDs
Public title
A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors
Scientific title
A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors
Secondary ID [1] 0 0
2011-005875-17
Secondary ID [2] 0 0
CMEK162X2110
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors Harboring a BRAF V600 Mutation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LGX818
Treatment: Drugs - MEK162
Treatment: Drugs - LEE011

Experimental: dual combination - LGX818 QD and MEK162 BID

Experimental: triple combination - LGX818 QD and MEK162 BID and LEE011 QD 3 weeks on, 1 week off.


Treatment: Drugs: LGX818


Treatment: Drugs: MEK162


Treatment: Drugs: LEE011


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase Ib: Estimation of Maximum Tolerated Dose (MTD) by measuring incidence of dose limiting toxicities (DLT) - To estimate the MTD(s) and/or recommended phase 2 dose(s) (RP2D(s)) of oral LGX818 in combination with oral MEK162, and of oral LGX818 in combination with oral MEK162 and oral LEE011 in patients with BRAF V600-dependent advanced solid tumors by measuring the incidence of DLTs as defined by the protocol.
Timepoint [1] 0 0
up to 8 months
Primary outcome [2] 0 0
Phase II: Clinical efficacy - Assess clinical efficacy of the LGX818 and MEK162 dual combination and LGX818 and MEK162 and LEE011 triple combination in the Phase II populations by evaluating the disease control rate (DCR) and objective response rate (ORR) as per RECIST 1.1
Timepoint [2] 0 0
up to 14 months
Secondary outcome [1] 0 0
Safety and tolerability of LGX818 and MEK162 dual combination, and LGX818 and MEK162 and LEE011 triple combination by evaluating the incidence and severity of adverse events (AE). - To characterize the safety and tolerability of LGX818 and MEK162 in combination, and LGX818 and MEK162 and LEE011 in combination by evaluating the incidence and severity (as per CTCAE grading) of AEs in all patients enrolled in the study.
Timepoint [1] 0 0
up to 17 months
Secondary outcome [2] 0 0
Determination of single and multiple dose of Pharmacokinetics (PK) profile by measuring plasma concentrations versus time after study drug combination dosing (Phase Ib) - To determine the single and multiple dose PK profile of the LGX818 and MEK162 combination and LGX818 and MEK162 and LEE011 combination, by measuring plasma concentrations of MEK162 and LGX818 and LEE011 resp. at different timepoints prior and post study drug combination dosing on several days within cycle 1 and subsequent cycles.
Timepoint [2] 0 0
up to 8 months
Secondary outcome [3] 0 0
Preliminary clinical anti-tumor activity by evaluating the objective response rate (Phase Ib) - To assess preliminary anti-tumor activity of the LGX818 and MEK162 combination, and the LGX818 and MEK162 and LEE011 combination by evaluating the ORR as per RECIST 1.1. Safety Issue?: (FDAAA) No
Timepoint [3] 0 0
up to 8 months
Secondary outcome [4] 0 0
Further clinical efficacy (phase II) - To further assess clinical efficacy of the LGX818 and MEK162 combination and the LGX818 and MEK162 and LEE011 combination in the Phase II populations by measuring progression free survival (PFS) as per RECIST 1.1
Timepoint [4] 0 0
up to 14 months

Eligibility
Key inclusion criteria
Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB
to IV per American Joint Committee on Cancer [AJCC]), or confirmed diagnosis of
non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon
agreement with the Sponsor, whose disease has progressed despite previous antineoplastic
therapy or for whom no further effective standard therapy is available

- Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation

- Evidence of measurable disease as determined by RECIST v1.1

- World Health Organization (WHO) Performance Status = 2

- Negative serum pregnancy test within 72 hours prior to the first study dose in all
women of childbearing potential
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Progressive disease following prior treatment with RAF-inhibitors in combination with
MEK-inhibitors

- Symptomatic or untreated leptomeningeal disease

- Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing
anti-epileptic drugs

- Known acute or chronic pancreatitis

- History or current evidence of retinal disease, retinal vein occlusion or
ophthalmopathy

- Clinically significant cardiac disease

- Patients with abnormal laboratory values at Screening/baseline

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LGX818/MEK162

- Previous or concurrent malignancy

- Pregnant or nursing (lactating) women

- For addition of LEE011 in the triple combination, congenital long QT syndrome or
family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade = 3,
brain metastases at baseline, abnormal coagulation results PT/INR >1.5 x ULN or aPTT
>1.5 x ULN.

Other protocol-defined inclusion/exclusion criteria may apply

Study design
Purpose of the study
Other
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
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Array BioPharma Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Array BioPharma Investigative Site - North Sydney
Recruitment hospital [3] 0 0
Array BioPharma Investigative Site - Westmead
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Maryland
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Cedex 10
Country [8] 0 0
Italy
State/province [8] 0 0
MI
Country [9] 0 0
Italy
State/province [9] 0 0
Napoli
Country [10] 0 0
Singapore
State/province [10] 0 0
Singapore
Country [11] 0 0
Spain
State/province [11] 0 0
Catalunya
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
Switzerland
State/province [13] 0 0
St. Gallen
Country [14] 0 0
Switzerland
State/province [14] 0 0
Zuerich

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate
the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple
combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part
to assess the clinical efficacy and to further assess the safety of the combinations in
selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous
schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off
schedule. Patients will be treated until progression of disease, unacceptable toxicity
develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28
days. The dose escalation parts of the trial will be conducted in adult patients with BRAF
V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the
dual combination and at least 12 patients for the triple combination. The dose escalation
will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D
declaration, patients will be enrolled in three Phase II arms for the dual combination and
one Phase II arm for the triple combination. All patients will be followed for 30 days for
safety assessments after study drugs discontinuation. All patients enrolled in the Phase II
part of the study will be followed for survival.
Trial website
https://clinicaltrials.gov/show/NCT01543698
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Array BioPharma Clinical Trial Call Center
Address 0 0
Array BioPharma
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
Other publications