Back to resultsA Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
Primary Purpose
Melanoma and Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
LGX818
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma and Metastatic Colorectal Cancer focused on measuring BRAF mutant,, BRAF mutated,, melanoma,, metastatic,, advanced,, RAF kinase inhibitor, BRAF V600 mutation
Eligibility Criteria
Inclusion Criteria:
For the dose escalation phase:
- 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.
- Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
- Evidence of measurable disease
Exclusion Criteria:
- Previous therapy with a MEK inhibitor.
- Symptomatic or untreated leptomeningeal disease.
- 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.
- Known acute or chronic pancreatitis.
- Clinically significant cardiac disease
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
- 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.
- 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).
- History of thromboembolic or cerebrovascular events within the last 6 months
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- H Lee Moffitt Cancer Center and Research Institute
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Beth Israel Deaconess Medical Center
- Dana-Farber Cancer Institute
- Western Sydney Local Health District
- Westmead Hospital- Redbank Rd
- Peter MacCallum Cancer Centre
- EDOG - Institut Claudia Regaud - PPDS
- EDOG - Institut Claudius Regaud - PPDS
- Institut Gustave Roussy
- Institut Gustave Roussy
- Institut Gustave Roussy
- Institut Gustave Roussy
- Institut Gustave Roussy
- National Cancer Center Hospital
- Oslo Myeloma Center - PPDS
- Hospital Clinic de Barcelona
- Hospital General Vall d'Hebron
- Hospital Universitario Vall d'Hebron - PPDS
- Hospital Universitario Vall d'Hebron
- Hospital Universitario Vall d'Hebron - PPDS
- Hospital Universitario HM Sanchinarro_CIOCC
- START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
- Kantonsspital Graubünden
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
LGX818 - Dose escalation
LGX818 - Dose Expansion at MTD or RP2D
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Dose Limiting Toxicities
Secondary Outcome Measures
Number and nature of Adverse events and clinical activity
Pharmacokinetic profile of LGX818
LGX818 Plasma concentration
Tumor response per RECIST
This includes duration of response, time to response, progression free survival and overall survival.
Baseline molecular status
Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01436656
Brief Title
A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
Official Title
A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 5, 2011 (Actual)
Primary Completion Date
October 1, 2012 (Actual)
Study Completion Date
November 7, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma and Metastatic Colorectal Cancer
Keywords
BRAF mutant,, BRAF mutated,, melanoma,, metastatic,, advanced,, RAF kinase inhibitor, BRAF V600 mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
93 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LGX818 - Dose escalation
Arm Type
Experimental
Arm Title
LGX818 - Dose Expansion at MTD or RP2D
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LGX818
Primary Outcome Measure Information:
Title
Incidence of Dose Limiting Toxicities
Time Frame
Approximately every 8 weeks (up to 2 years)
Secondary Outcome Measure Information:
Title
Number and nature of Adverse events and clinical activity
Time Frame
Approximately 3 years
Title
Pharmacokinetic profile of LGX818
Description
LGX818 Plasma concentration
Time Frame
Approximately 2 years
Title
Tumor response per RECIST
Description
This includes duration of response, time to response, progression free survival and overall survival.
Time Frame
Approximately 3 years
Title
Baseline molecular status
Description
Baseline molecular status (mutation/ amplification/ expression) in tumor tissue of potential predictive markers
Time Frame
Approximately 3 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
For the dose escalation phase:
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.
Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
Evidence of measurable disease
Exclusion Criteria:
Previous therapy with a MEK inhibitor.
Symptomatic or untreated leptomeningeal disease.
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.
Known acute or chronic pancreatitis.
Clinically significant cardiac disease
Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818
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.
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).
History of thromboembolic or cerebrovascular events within the last 6 months
Other protocol-defined inclusion/exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
H Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Western Sydney Local Health District
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Westmead Hospital- Redbank Rd
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
East Melbourne
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
EDOG - Institut Claudia Regaud - PPDS
City
Toulouse
State/Province
Haute-garonne
ZIP/Postal Code
31059 Cedex 9
Country
France
Facility Name
EDOG - Institut Claudius Regaud - PPDS
City
Toulouse
State/Province
Haute-garonne
ZIP/Postal Code
31059 Cedex 9
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
State/Province
ILE DE France - VAL DE Marne (94)
ZIP/Postal Code
94800
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
State/Province
VAL DE Marne
ZIP/Postal Code
94800
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif Cedex
State/Province
Val-de-marne
ZIP/Postal Code
94805
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
State/Province
Val-de-marne
ZIP/Postal Code
94805
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Oslo Myeloma Center - PPDS
City
Oslo
ZIP/Postal Code
00424
Country
Norway
Facility Name
Hospital Clinic de Barcelona
City
Badalona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital General Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron - PPDS
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario Vall d'Hebron - PPDS
City
Barcelona
ZIP/Postal Code
8035
Country
Spain
Facility Name
Hospital Universitario HM Sanchinarro_CIOCC
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
City
Madrid
ZIP/Postal Code
28050
Country
Spain
Facility Name
Kantonsspital Graubünden
City
Chur
State/Province
Graubünden (DE)
ZIP/Postal Code
07000
Country
Switzerland
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Learn more about this trial
A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
We'll reach out to this number within 24 hrs