Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
A Phase Ib/II Multi-center, Open-label, Dose Escalation Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in Patients With BRAF Mutant Metastatic Colorectal Cancer
3 other identifiers
interventional
156
12 countries
52
Brief Summary
This study will assess the safety and efficacy of LGX818 when combined with cetuximab or combined with cetuximab and BYL719 in patients with BRAF mutant metastatic colorectal cancer
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 colorectal-cancer
Started Nov 2012
Longer than P75 for phase_2 colorectal-cancer
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2012
CompletedFirst Posted
Study publicly available on registry
November 1, 2012
CompletedStudy Start
First participant enrolled
November 23, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 31, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
February 12, 2019
CompletedResults Posted
Study results publicly available
June 23, 2021
CompletedJune 23, 2021
May 1, 2021
2.9 years
October 30, 2012
April 12, 2021
May 26, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
DLTs were defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment and meets any of the criteria included blood and lymphatic system disorders, investigations (blood, renal, hepatic, metabolic), skin and subcutaneous tissue disorders: rash, HFSR (hand foot skin reaction) and/or photosensitivity, metabolism and nutrition disorders: hyperglycemia, gastrointestinal disorders, cardiac disorders, vascular disorders, general disorders and administration site conditions, tumor lysis syndrome, ophthalmologic and other adverse events: study drug-related fever, alkaline phosphatase elevation.
Cycle 1: Day 1 to Day 28
Phase 2: Progression Free Survival (PFS)
PFS was defined as the time from the date of randomization to the date of the first documented disease progression or death due to any cause. Participants who did not progress per RECIST (Response Evaluation Criteria in Solid Tumors) version (v) 1.1, were not known to have died prior to the data cut-off, or received any further anticancer therapy were censored at the date of last adequate tumor assessment or the anticancer therapy date, whichever was earlier.
From the date of randomization until the first documentation of disease progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)
Secondary Outcomes (25)
Number of Participants With Treatment - Emergent Adverse Events of Grade 3 or 4 Severity Based on National Cancer Institute of Common Terminology Criteria (NCI-CTCAE), Version 4.0
From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately)
Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
- +20 more secondary outcomes
Study Arms (2)
LGX818 + cetuximab
EXPERIMENTALLGX818 + BYL719 + cetuximab
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- Metastatic colorectal cancer
- Progression after at least one prior standard of care regimen or be intolerant to irinotecan-based regimens
- Life expectancy ≥ 3 months
- ECOG performance status ≤ 2
You may not qualify if:
- Symptomatic or untreated leptomeningeal disease
- Symptomatic brain metastasis
- Patients with clinically manifested diabetes
- Acute or chronic pancreatitis
- Clinically significant cardiac disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (52)
Keck Hospital of USC
Los Angeles, California, 90033, United States
LAC&USC Medical Center
Los Angeles, California, 90033, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
UCLA University of California Los Angeles
Los Angeles, California, 90095, United States
Westwood Bowyer Clinic, Peter Morton Medical Building
Los Angeles, California, 90095, United States
UCLA Hematology Oncology
Santa Monica, California, 90404, United States
UCLA Santa Monica Medical Center & Orthopaedic Hospital
Santa Monica, California, 90404, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, 06510, United States
Yale University
New Haven, Connecticut, 06520, United States
Smilow Cancer Hospital Care Center at North Haven
North Haven, Connecticut, 06473, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114-2620, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10017-6706, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10022, United States
Tennessee Oncology, PLLC
Dickson, Tennessee, 37055, United States
Tennessee Oncology, PLLC
Franklin, Tennessee, 37067, United States
Tennessee Oncology, PLLC
Gallatin, Tennessee, 37066, United States
Tennessee Oncology, PLLC
Hermitage, Tennessee, 37076, United States
Tennessee Oncology, PLLC
Lebanon, Tennessee, 37909, United States
Tennessee Oncology, PLLC
Murfreesboro, Tennessee, 37129, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37205, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37207, United States
Tennessee Oncology, PLLC
Nashville, Tennessee, 37211, United States
Tennessee Oncology, PLLC
Shelbyville, Tennessee, 37160, United States
Tennessee Oncology, PLLC
Smyrna, Tennessee, 37167, United States
University of Utah - Huntsman Cancer Institute - PPDS
Salt Lake City, Utah, 84112-5550, United States
Huntsman Cancer Hospital
Salt Lake City, Utah, 84112, United States
Redwood Health Center - ARUP Lab Draw Location
Salt Lake City, Utah, 84119, United States
John A Moran Eye Center
Salt Lake City, Utah, 84132, United States
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
UZ Gasthuisberg
Leuven, Vlaams Brabant, 3000, Belgium
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Sir Mortimer B. Davis Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
Montpellier, 34298, France
EDOG - Institut Claudius Regaud - PPDS
Toulouse, 31052, France
University Hospital of Koln
Cologne, North Rhine-Westphalia, 50937, Germany
Universitätsklinikum Essen
Essen, 45147, Germany
Ospedaliero Universitaria di Modena Policlinico
Modena, 41100, Italy
Pharmacy of National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045, Japan
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Amsterdam, North Holland, 1066 CX, Netherlands
Erasmus MC
Rotterdam, South Holland, 3015 CE, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Oslo Myeloma Center - PPDS
Oslo, 0379, Norway
Samsung Medical Center - PPDS
Gangnam-Gu, Seoul Teugbyeolsi, 06351, South Korea
Asan Medical Center - PPDS
Songpa-Gu, Seoul Teugbyeolsi, 05505, South Korea
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
Barcelona, 08035, Spain
Hospital Universitario 12 de Octubre
Madrid, 28026, Spain
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41013, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 30, 2012
First Posted
November 1, 2012
Study Start
November 23, 2012
Primary Completion
October 31, 2015
Study Completion
February 12, 2019
Last Updated
June 23, 2021
Results First Posted
June 23, 2021
Record last verified: 2021-05
Data Sharing
- IPD Sharing
- Will share
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.