Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT01436656
Ethics application status
Date submitted
14/04/2011
Date registered
20/09/2011
Date last updated
28/10/2024

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
C4221010
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
Experimental: LGX818 - Dose escalation -

Experimental: LGX818 - Dose Expansion at MTD or RP2D -

Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase
Timepoint [1] 0 0
Up to 28 days
Primary outcome [2] 0 0
Number of Participants With DLT During Dose Expansion Phase
Timepoint [2] 0 0
Up to 28 days
Secondary outcome [1] 0 0
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase
Timepoint [1] 0 0
From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)
Secondary outcome [2] 0 0
Number of Participants With AEs and SAEs During Dose Expansion Phase
Timepoint [2] 0 0
From start of study treatment until 30 days after last dose of study treatment (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Secondary outcome [3] 0 0
Progression Free Survival (PFS): Dose Escalation Phase
Timepoint [3] 0 0
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
Secondary outcome [4] 0 0
PFS: Dose Expansion Phase
Timepoint [4] 0 0
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Secondary outcome [5] 0 0
Duration of Response (DOR): Dose Escalation Phase
Timepoint [5] 0 0
From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)
Secondary outcome [6] 0 0
Time to Response (TTR): Dose Escalation Phase
Timepoint [6] 0 0
From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)
Secondary outcome [7] 0 0
DOR: Dose Expansion Phase
Timepoint [7] 0 0
From first observation of response until first time of PD or death due to any cause (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Secondary outcome [8] 0 0
TTR: Dose Expansion Phase
Timepoint [8] 0 0
From date of start of treatment until CR or PR or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Secondary outcome [9] 0 0
Overall Survival (OS): Dose Expansion Phase
Timepoint [9] 0 0
From start of study treatment until date of death or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)
Secondary outcome [10] 0 0
Maximum Observed Plasma Concentration of LGX818: Dose Escalation Phase
Timepoint [10] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [11] 0 0
Time Point of Maximum Concentration (Tmax) of LGX818: Dose Escalation Phase
Timepoint [11] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [12] 0 0
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of LGX818: Dose Escalation Phase
Timepoint [12] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [13] 0 0
Area Under the Concentration-Time Curve From Time Zero to Tau (AUCtau) of LGX818: Dose Escalation Phase
Timepoint [13] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [14] 0 0
Elimination Half-life (t1/2) of LGX818: Dose Escalation Phase
Timepoint [14] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [15] 0 0
Apparent Total Plasma Clearance of Drug (CL/F) of LGX818: Dose Escalation Phase
Timepoint [15] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [16] 0 0
Apparent Volume of Distribution (Vz/F) of LGX818: Dose Escalation Phase
Timepoint [16] 0 0
Pre-dose (0 hour), 0.5, 3, 4, 6, 8, 10 (only for BID arms), 24 hours post dose on Day 1 and 15 of Cycle 1 (each cycle=28 days)
Secondary outcome [17] 0 0
Number of Participants According to Tumor Response Per RECIST Criteria- Dose Escalation
Timepoint [17] 0 0
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 556.1 weeks of treatment exposure)
Secondary outcome [18] 0 0
Maximum Observed Plasma Concentration of LGX818: Dose Expansion Phase
Timepoint [18] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [19] 0 0
Vz/F of LGX818: Dose Expansion Phase
Timepoint [19] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [20] 0 0
Tmax of LGX818: Dose Expansion Phase
Timepoint [20] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [21] 0 0
AUCinf of LGX818: Dose Expansion Phase
Timepoint [21] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [22] 0 0
AUCtau of LGX818: Dose Expansion Phase
Timepoint [22] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [23] 0 0
t1/2 of LGX818: Dose Expansion Phase
Timepoint [23] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [24] 0 0
CL/F of LGX818: Dose Expansion Phase
Timepoint [24] 0 0
Predose (0 hour), 0.5, 2, 4, 6, 8, 24 hours post dose on Day 1,8 and 15 of Cycle 1 (cycle=28 days)
Secondary outcome [25] 0 0
Number of Participants According to BRAF V600 Mutation Status at Baseline: Dose Expansion
Timepoint [25] 0 0
(Baseline) last non-missing value prior to the first dose (Baseline)
Secondary outcome [26] 0 0
Number of Participants According to Tumor Response Per RECIST Criteria: Dose Expansion
Timepoint [26] 0 0
From start of study treatment until first documentation of PD or death due to any cause or censoring date (maximum of 257.3 weeks and 114.6 weeks of treatment exposure for melanoma participants and mCRC participants respectively)

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
Sex
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
Completed
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
Actual
7/11/2022
Sample size
Target
Accrual to date
Final
107
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Western Sydney Local Health District - Westmead
Recruitment hospital [2] 0 0
Westmead Hospital- Redbank Rd - Westmead
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
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
Haute-garonne
Country [4] 0 0
France
State/province [4] 0 0
ILE DE France - VAL DE Marne (94)
Country [5] 0 0
France
State/province [5] 0 0
VAL DE Marne
Country [6] 0 0
France
State/province [6] 0 0
Val-de-marne
Country [7] 0 0
France
State/province [7] 0 0
Villejuif
Country [8] 0 0
Japan
State/province [8] 0 0
Tokyo
Country [9] 0 0
Norway
State/province [9] 0 0
Oslo
Country [10] 0 0
Spain
State/province [10] 0 0
Badalona
Country [11] 0 0
Spain
State/province [11] 0 0
Barcelona
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
Switzerland
State/province [13] 0 0
Graubünden (DE)
Country [14] 0 0
Switzerland
State/province [14] 0 0
Zürich

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/study/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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01436656