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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01436656




Registration number
NCT01436656
Ethics application status
Date submitted
14/04/2011
Date registered
20/09/2011
Date last updated
18/06/2020

Titles & IDs
Public title
A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
Scientific title
A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
Secondary ID [1] 0 0
2011-000556-42
Secondary ID [2] 0 0
CLGX818X2101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma and Metastatic Colorectal Cancer 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 - LGX818

Experimental: LGX818 - Dose escalation -

Experimental: LGX818 - Dose Expansion at MTD or RP2D -


Treatment: Drugs: LGX818
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of Dose Limiting Toxicities
Timepoint [1] 0 0
Approximately every 8 weeks (up to 2 years)
Secondary outcome [1] 0 0
Number and nature of Adverse events and clinical activity
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
Pharmacokinetic profile of LGX818 - LGX818 Plasma concentration
Timepoint [2] 0 0
Approximately 2 years
Secondary outcome [3] 0 0
Tumor response per RECIST - This includes duration of response, time to response, progression free survival and overall survival.
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
Baseline molecular status - Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers
Timepoint [4] 0 0
Approximately 3 years

Eligibility
Key inclusion criteria
For the dose escalation phase:

1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage
IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion
phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic
melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii)
confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC)
for which no further effective standard therapy exists.

2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.

3. Evidence of measurable disease
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous therapy with a MEK inhibitor.

2. Symptomatic or untreated leptomeningeal disease.

3. Symptomatic or untreated brain metastasis.Patients previously treated for these
conditions that are asymptomatic in the absence of corticosteroid therapy are allowed
to enroll. Brain metastasis must be stable with verification by imaging.

4. Known acute or chronic pancreatitis.

5. Clinically significant cardiac disease

6. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LGX818

7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include:
adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the
cervix, treated curatively and without evidence of recurrence for at least 3 years
prior to study entry; or other solid tumor treated curatively, and without evidence of
recurrence for at least 3 years prior to study entry.

8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL).

9. History of thromboembolic or cerebrovascular events within the last 6 months

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
Single group
Other design features
Phase
Phase 1
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
5/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2021
Actual
Sample size
Target
Accrual to date
Final
107
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Pfizer Investigative Site - Westmead
Recruitment hospital [2] 0 0
Pfizer Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3050 - Parkville
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
Massachusetts
Country [3] 0 0
France
State/province [3] 0 0
Toulouse Cedex 9
Country [4] 0 0
France
State/province [4] 0 0
Villejuif Cedex
Country [5] 0 0
Japan
State/province [5] 0 0
Tokyo
Country [6] 0 0
Norway
State/province [6] 0 0
Oslo
Country [7] 0 0
Spain
State/province [7] 0 0
Catalunya
Country [8] 0 0
Spain
State/province [8] 0 0
Madrid
Country [9] 0 0
Switzerland
State/province [9] 0 0
Chur
Country [10] 0 0
Switzerland
State/province [10] 0 0
Zuerich

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

Ethics approval
Ethics application status

Summary
Brief summary
CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose
(MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily
and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic
melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase)
and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the
expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts
of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion
part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.
Trial website
https://clinicaltrials.gov/show/NCT01436656
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
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