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Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer

Primary Purpose

Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LGX818
Cetuximab
BYL719
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring Open-label dose escalation, BRAF inhibitor, LGX818, PI3K inhibitor, BYL719, EGFR, cetuximab, metastatic colorectal cancer, KRAS, BRAF, V600

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Keck Hospital of USC
  • LAC&USC Medical Center
  • USC/Norris Comprehensive Cancer Center
  • Ronald Reagan UCLA Medical Center
  • UCLA University of California Los Angeles
  • Westwood Bowyer Clinic, Peter Morton Medical Building
  • UCLA Hematology Oncology
  • UCLA Santa Monica Medical Center & Orthopaedic Hospital
  • Smilow Cancer Hospital at Yale-New Haven
  • Yale University
  • Smilow Cancer Hospital Care Center at North Haven
  • Massachusetts General Hospital
  • Hackensack University Medical Center
  • John Theurer Cancer Center at Hackensack University Medical Center
  • Memorial Sloan-Kettering Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • Tennessee Oncology, PLLC
  • University of Utah - Huntsman Cancer Institute - PPDS
  • Huntsman Cancer Hospital
  • Redwood Health Center - ARUP Lab Draw Location
  • John A Moran Eye Center
  • Royal Melbourne Hospital
  • UZ Gasthuisberg
  • Princess Margaret Cancer Centre
  • Sir Mortimer B. Davis Jewish General Hospital
  • Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
  • EDOG - Institut Claudius Regaud - PPDS
  • University Hospital of Koln
  • Universitätsklinikum Essen
  • Ospedaliero Universitaria di Modena Policlinico
  • Pharmacy of National Cancer Center Hospital East
  • National Cancer Center Hospital
  • Samsung Medical Center - PPDS
  • Asan Medical Center - PPDS
  • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
  • Erasmus MC
  • Universitair Medisch Centrum Utrecht
  • Oslo Myeloma Center - PPDS
  • Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
  • Hospital Universitario 12 de Octubre
  • Hospital Universitario Virgen del Rocio - PPDS

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

LGX818 + cetuximab

LGX818 + BYL719 + cetuximab

Arm Description

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
An AE was any untoward medical occurrence attributed to study drug in participants who received study drug. As per NCI-CTCAE v4.0, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to study drug. Treatment-emergent AEs are between first dose of study drug and up to 30 days after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. Number of participants with any Grade 3 or 4 treatment-emergent AE were reported in this outcome measure.
Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib)
Volume of distribution at steady state is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib)
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib)
Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib)
Tmax was defined as the time to reach maximum observed plasma concentration of encorafenib.
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib)
Tmax, ss was defined as the time to reach maximum observed plasma concentration of LGX818 (encorafenib) at steady state.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib)
Tmax was defined as the time to reach maximum observed plasma concentration of alpelisib.
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib)
Tmax, ss was defined as the time to reach maximum observed plasma concentration of BYL719 (alpelisib) at steady state.
Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib)
T-last was defined as the time to reach last observed plasma concentration of encorafenib.
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib)
T-last, ss was defined as the time to reach last observed plasma concentration of encorafenib at steady state.
Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib)
T-last was defined as the time to reach last observed plasma concentration of alpelisib.
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib)
T-last, ss was defined as the time to reach last observed plasma concentration of alpelisib at steady state.
Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib)
Ctrough, ss was defined as plasma trough concentration of encorafenib at steady state.
Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib)
Ctrough, ss was defined as plasma trough concentration of alpelisib at steady state.
Overall Survival (OS)
OS was defined as the time (in months) 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. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Overall Response Rate (ORR)
Overall response rate as assessed by the investigator per RECIST v1.1, was defined as percentage of participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-nodal target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Only confirmed CR and PR are counted (those confirmed at least 4 weeks).
Duration of Response (DOR)
DOR: Time between date of the first documented response (CR or PR) and the date of first documented PD or death due to underlying cancer. If PD or death due to underlying cancer not occurred, then participant was censored at the date of last tumor assessment other than unknown. DOR was calculated for responders (confirmed) only. CR: Disappearance of all target, non-target lesions sustained for >=4 weeks and any pathological lymph nodes reduced in short axis to <10mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameter. PD for target lesions: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm, or appearance of >=1 new lesions. PD for non-target lesions: Unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy or appearance of new unequivocal malignant lesion.
Time to Response (TTR)
TTR as assessed by investigator according to RECIST v1.1, was defined as the time (in months) from date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival.
Phase 1b: Progression Free Survival (PFS)
PFS was defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. Participants who did not progress per RECIST v1.1, 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.
Phase 2: Number of Participants With Any Variant in Gene Status at Baseline
Gene alterations/expression relevant to the RAF/MEK/ERK (proto-oncogene serine/threonine-protein kinase/ mitogen-activated ERK kinase/ extracellular signal-regulated kinases) and EGFR/PI3K/AKT (epidermal growth factor receptor/ phosphatidylinositol 3-kinase/ protein kinase B) pathways in tumor tissue, baseline molecular status (mutation/amplification/expression) in tumor tissue of potential predictive markers of tumor response or resistance i.e. BRAF (v-raf murine sarcoma viral oncogene homolog B1), HRAS (harvey rat sarcoma protein), KRAS (V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog B1), NRAS (neuroblastoma RAS viral oncogene homolog), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol 3-kinase gene), MAP2K1 (mitogen-activated protein kinase 1), MAP2K2 (mitogen-activated protein kinase 2), ARAF, c-MET, RAF1, EGFR was analyzed.

Full Information

First Posted
October 30, 2012
Last Updated
May 26, 2021
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01719380
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
November 23, 2012 (Actual)
Primary Completion Date
October 31, 2015 (Actual)
Study Completion Date
February 12, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
Open-label dose escalation, BRAF inhibitor, LGX818, PI3K inhibitor, BYL719, EGFR, cetuximab, metastatic colorectal cancer, KRAS, BRAF, V600

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
156 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LGX818 + cetuximab
Arm Type
Experimental
Arm Title
LGX818 + BYL719 + cetuximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LGX818
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Type
Drug
Intervention Name(s)
BYL719
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Incidence of Dose Limiting Toxicities (DLTs): Cycle 1
Description
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.
Time Frame
Cycle 1: Day 1 to Day 28
Title
Phase 2: Progression Free Survival (PFS)
Description
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.
Time Frame
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 Outcome Measure Information:
Title
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
Description
An AE was any untoward medical occurrence attributed to study drug in participants who received study drug. As per NCI-CTCAE v4.0, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to study drug. Treatment-emergent AEs are between first dose of study drug and up to 30 days after last dose of study drug, that were absent before treatment or that worsened relative to pretreatment state. Number of participants with any Grade 3 or 4 treatment-emergent AE were reported in this outcome measure.
Time Frame
From screening up to 30 days after the last dose of study treatment (for a maximum duration of 43 months, approximately)
Title
Apparent Total Plasma Clearance (CL/F) of LGX818 (Encorafenib)
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of LGX818 (Encorafenib)
Description
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Total Plasma Clearance (CL/F) of BYL719 (Alpelisib)
Description
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Total Plasma Clearance at Steady State (CL/F, ss) of BYL719 (Alpelisib)
Description
Clearance of a drug at steady state is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Terminal Volume of Distribution (Vz/F) of LGX818 (Encorafenib)
Description
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of LGX818 (Encorafenib)
Description
Volume of distribution at steady state is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Terminal Volume of Distribution (Vz/F) of BYL719 (Alpelisib)
Description
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Apparent Terminal Volume of Distribution at Steady State (Vz/F, ss) of BYL719 (Alpelisib)
Description
Volume of distribution at steady state was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F, ss) is influenced by the fraction absorbed.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of LGX818 (Encorafenib)
Description
Tmax was defined as the time to reach maximum observed plasma concentration of encorafenib.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of LGX818 (Encorafenib)
Description
Tmax, ss was defined as the time to reach maximum observed plasma concentration of LGX818 (encorafenib) at steady state.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of BYL719 (Alpelisib)
Description
Tmax was defined as the time to reach maximum observed plasma concentration of alpelisib.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time to Reach Maximum Plasma Concentration at Steady State (Tmax, ss) of BYL719 (Alpelisib)
Description
Tmax, ss was defined as the time to reach maximum observed plasma concentration of BYL719 (alpelisib) at steady state.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time of Last Observed Plasma Concentration (T-last) of LGX818 (Encorafenib)
Description
T-last was defined as the time to reach last observed plasma concentration of encorafenib.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of LGX818 (Encorafenib)
Description
T-last, ss was defined as the time to reach last observed plasma concentration of encorafenib at steady state.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time of Last Observed Plasma Concentration (T-last) of BYL719 (Alpelisib)
Description
T-last was defined as the time to reach last observed plasma concentration of alpelisib.
Time Frame
Cycle 1 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Time of Last Observed Plasma Concentration at Steady State (T-last, ss) of BYL719 (Alpelisib)
Description
T-last, ss was defined as the time to reach last observed plasma concentration of alpelisib at steady state.
Time Frame
Cycle 1 Day 8, Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Plasma Trough Concentration at Steady State (Ctrough, ss) of LGX818 (Encorafenib)
Description
Ctrough, ss was defined as plasma trough concentration of encorafenib at steady state.
Time Frame
Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Plasma Trough Concentration at Steady State (Ctrough, ss) of BYL719 (Alpelisib)
Description
Ctrough, ss was defined as plasma trough concentration of alpelisib at steady state.
Time Frame
Cycle 2 Day 1: Pre-dose, 0.5, 1, 2, 4, 6, 8 and 24 +/- 2 hours post-dose
Title
Overall Survival (OS)
Description
OS was defined as the time (in months) 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. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Time Frame
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)
Title
Overall Response Rate (ORR)
Description
Overall response rate as assessed by the investigator per RECIST v1.1, was defined as percentage of participants with a best overall response of complete response (CR) or partial response (PR), were recorded from date of randomization or date of start of treatment until date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target and non-nodal target lesions, and sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Only confirmed CR and PR are counted (those confirmed at least 4 weeks).
Time Frame
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)
Title
Duration of Response (DOR)
Description
DOR: Time between date of the first documented response (CR or PR) and the date of first documented PD or death due to underlying cancer. If PD or death due to underlying cancer not occurred, then participant was censored at the date of last tumor assessment other than unknown. DOR was calculated for responders (confirmed) only. CR: Disappearance of all target, non-target lesions sustained for >=4 weeks and any pathological lymph nodes reduced in short axis to <10mm. PR: >=30% decrease in sum of diameters of target lesions, taking as reference baseline sum of diameter. PD for target lesions: At least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm, or appearance of >=1 new lesions. PD for non-target lesions: Unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy or appearance of new unequivocal malignant lesion.
Time Frame
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)
Title
Time to Response (TTR)
Description
TTR as assessed by investigator according to RECIST v1.1, was defined as the time (in months) from date of randomization or date of start of treatment until first documented response (CR or PR) or data censoring date, whichever occurred first. CR was defined as complete disappearance of all target and non-target lesions sustained for at least 4 weeks apart before progression. Any pathological lymph nodes (whether target or non-target) reduced in short axis to <10 mm. PR was defined as at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants who did not achieve a confirmed PR or CR, were censored at last adequate tumor assessment date when they did not progress (including deaths not due to underlying disease) or at maximum follow-up (from study start to study end date) when participant had an event for progression-free survival.
Time Frame
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)
Title
Phase 1b: Progression Free Survival (PFS)
Description
PFS was defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. Participants who did not progress per RECIST v1.1, 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.
Time Frame
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)
Title
Phase 2: Number of Participants With Any Variant in Gene Status at Baseline
Description
Gene alterations/expression relevant to the RAF/MEK/ERK (proto-oncogene serine/threonine-protein kinase/ mitogen-activated ERK kinase/ extracellular signal-regulated kinases) and EGFR/PI3K/AKT (epidermal growth factor receptor/ phosphatidylinositol 3-kinase/ protein kinase B) pathways in tumor tissue, baseline molecular status (mutation/amplification/expression) in tumor tissue of potential predictive markers of tumor response or resistance i.e. BRAF (v-raf murine sarcoma viral oncogene homolog B1), HRAS (harvey rat sarcoma protein), KRAS (V-Ki-ras2 kirsten rat sarcoma viral oncogene homolog B1), NRAS (neuroblastoma RAS viral oncogene homolog), PTEN (phosphatase and tensin homolog), PIK3CA (phosphatidylinositol 3-kinase gene), MAP2K1 (mitogen-activated protein kinase 1), MAP2K2 (mitogen-activated protein kinase 2), ARAF, c-MET, RAF1, EGFR was analyzed.
Time Frame
Baseline (Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
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
Keck Hospital of USC
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
LAC&USC Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Westwood Bowyer Clinic, Peter Morton Medical Building
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UCLA Hematology Oncology
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
UCLA Santa Monica Medical Center & Orthopaedic Hospital
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Smilow Cancer Hospital at Yale-New Haven
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Smilow Cancer Hospital Care Center at North Haven
City
North Haven
State/Province
Connecticut
ZIP/Postal Code
06473
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114-2620
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10017-6706
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10022
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Dickson
State/Province
Tennessee
ZIP/Postal Code
37055
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Franklin
State/Province
Tennessee
ZIP/Postal Code
37067
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Gallatin
State/Province
Tennessee
ZIP/Postal Code
37066
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Hermitage
State/Province
Tennessee
ZIP/Postal Code
37076
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Lebanon
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Murfreesboro
State/Province
Tennessee
ZIP/Postal Code
37129
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37207
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37211
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Shelbyville
State/Province
Tennessee
ZIP/Postal Code
37160
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Smyrna
State/Province
Tennessee
ZIP/Postal Code
37167
Country
United States
Facility Name
University of Utah - Huntsman Cancer Institute - PPDS
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112-5550
Country
United States
Facility Name
Huntsman Cancer Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Redwood Health Center - ARUP Lab Draw Location
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84119
Country
United States
Facility Name
John A Moran Eye Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
UZ Gasthuisberg
City
Leuven
State/Province
Vlaams Brabant
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Sir Mortimer B. Davis Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
EDOG - Institut Claudius Regaud - PPDS
City
Toulouse
ZIP/Postal Code
31052
Country
France
Facility Name
University Hospital of Koln
City
Köln
State/Province
Nordrhein-westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
Universitätsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Ospedaliero Universitaria di Modena Policlinico
City
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Pharmacy of National Cancer Center Hospital East
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277-8577
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Samsung Medical Center - PPDS
City
Gangnam-Gu
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Asan Medical Center - PPDS
City
Songpa-Gu
State/Province
Seoul Teugbyeolsi
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
City
Amsterdam
State/Province
Noord-holland
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
State/Province
Zuid-holland
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Oslo Myeloma Center - PPDS
City
Oslo
ZIP/Postal Code
0379
Country
Norway
Facility Name
Instituto de Investigacion Oncologica Vall d'Hebron (VHIO) - EPON
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
ZIP/Postal Code
28026
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio - PPDS
City
Sevilla
ZIP/Postal Code
41013
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
Yes
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.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

Learn more about this trial

Study of LGX818 and Cetuximab or LGX818, BYL719, and Cetuximab in BRAF Mutant Metastatic Colorectal Cancer

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