Clinical trial NCT01719380: Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Open-label dose escalation
BRAF inhibitor
LGX818
PI3K inhibitor
BYL719
EGFR
cetuximab
metastatic colorectal cancer
KRAS
BRAF
V600
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-11-01
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* Symptomatic or untreated leptomeningeal disease
* Symptomatic brain metastasis
* Patients with clinically manifested diabetes
* Acute or chronic pancreatitis
* Clinically significant cardiac disease

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
timeFrame: Cycle 1: Day 1 to Day 28
measure: Phase 2: Progression Free Survival (PFS)
timeFrame: 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:
measure: 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
timeFrame: From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately)
measure: Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib)
timeFrame: Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib)
timeFrame: Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib)
timeFrame: Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
measure: Overall Survival (OS)
timeFrame: From the date of randomization or date of start of treatment to the date of death due to any cause or data censoring date, whichever occurred first (up to 43 months)
measure: Overall Response Rate (ORR)
timeFrame: From date of randomization or date of start of treatment until date of first documentation of PD or death due to any cause (maximum up to 43 months)
measure: Duration of Response (DOR)
timeFrame: From the first documentation of OR (confirmed CR or PR) to first documentation of PD/death due to any cause or censoring date, whichever occurred first (up to 43 months)
measure: Time to Response (TTR)
timeFrame: From the date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first (maximum up to 43 months)
measure: Phase 1b: Progression Free Survival (PFS)
timeFrame: From date of start of treatment to the date of event defined as the first documented progression or death due to any cause, censored date, whichever occurred first (maximum up to 43 months)
measure: Phase 2: Number of Participants With Any Variant in Gene Status at Baseline
timeFrame: Baseline (Day 1)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC&USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA University of California Los Angeles
state: California
city: Los Angeles
country: United States
facility: Westwood Bowyer Clinic, Peter Morton Medical Building
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology Oncology
state: California
city: Santa Monica
country: United States
facility: UCLA Santa Monica Medical Center & Orthopaedic Hospital
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale-New Haven
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: North Haven
country: United States
facility: Smilow Cancer Hospital Care Center at North Haven
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Dickson
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Franklin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Gallatin
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Hermitage
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Lebanon
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Murfreesboro
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Shelbyville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Smyrna
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute - PPDS
state: Utah
city: Salt Lake City
country: United States
facility: Huntsman Cancer Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Redwood Health Center - ARUP Lab Draw Location
state: Utah
city: Salt Lake City
country: United States
facility: John A Moran Eye Center
state: Utah
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
state: Vlaams Brabant
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Quebec
city: Montpellier
country: France
facility: Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
city: Toulouse
country: France
facility: EDOG - Institut Claudius Regaud - PPDS
city: Köln
country: Germany
facility: University Hospital of Koln
state: Nordrhein-westfalen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Modena
country: Italy
facility: Ospedaliero Universitaria di Modena Policlinico
city: Kashiwa
country: Japan
facility: Pharmacy of National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Gangnam-Gu
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
state: Seoul Teugbyeolsi
city: Songpa-Gu
country: Korea, Republic of
facility: Asan Medical Center - PPDS
state: Seoul Teugbyeolsi
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
state: Noord-holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC
state: Zuid-holland
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Oslo
country: Norway
facility: Oslo Myeloma Center - PPDS
city: Barcelona
country: Spain
facility: Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: