Melanoma and Metastatic Colorectal CancerPhase 1NCT01436656
A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
A Phase 1 study testing LGX818 in people with Melanoma and Metastatic Colorectal Cancer, run by Pfizer at 24 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma and Metastatic Colorectal Cancer
- What is being tested?
- LGX818
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 24 sitesin 7 countries
- Study dates
- 5 Sep 2011to 7 Nov 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
24 sites in 7 countries.
24 sites in 7 countries
Spain7 sites
Hospital Clinic de Barcelona
Badalona, 08036
Hospital General Vall d'Hebron
Barcelona, 08035
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 08035
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 8035
Hospital Universitario HM Sanchinarro_CIOCC
Madrid, 28050
START MADRID_Hospital Universitario HM Sanchinarro - CIOCC
Madrid, 28050
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
France5 sites
EDOG - Institut Claudius Regaud - PPDS
Toulouse, Haute-garonne, 31059 Cedex 9
Institut Gustave Roussy
Villejuif, ILE de France - VAL de Marne (94), 94800
Institut Gustave Roussy
Villejuif, VAL DE Marne, 94800
Institut Gustave Roussy
Villejuif, Val-de-marne, 94805
Institut Gustave Roussy
Villejuif, 94805
Australia3 sites
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 3002
Western Sydney Local Health District
Westmead, New South Wales, 2145
Westmead Hospital- Redbank Rd
Westmead, New South Wales, 2145
Switzerland2 sites
Kantonsspital Graubünden
Chur, Graubünden (DE), 07000
Universität Zürich
Zurich, 8091
About this study
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
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.
- Being tested
- LGX818
- Keywords
- BRAF mutant,, BRAF mutated,, melanoma,, metastatic,, advanced,, RAF kinase inhibitor, BRAF V600 mutation
- Medical subject headings
- Melanoma, Colorectal Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LGX818Drug
| Study group | Role | What they receive |
|---|---|---|
| LGX818 - Dose escalation | Experimental | Not described Receives: Drug: LGX818 |
| LGX818 - Dose Expansion at MTD or RP2D | Experimental | Not described Receives: Drug: LGX818 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Measured: Up to 28 days
Number of Participants With DLT During Dose Expansion Phase
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Measured: Up to 28 days
Secondary outcomes (26)
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the participants general condition, any SAEs that were expected due to the condition being treated.
Measured: From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)
Number of Participants With AEs and SAEs During Dose Expansion Phase
An AE was defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions. An SAE was defined as one of the following: fatal or life-threatening; resulted in significant disability/incapacity; congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization unless for routine treatment, elective or pre-planned treatment for a pre-existing condition, treatment on an emergency outpatient basis, social reasons and respite care in the absence of any deterioration in the participants general condition, any SAEs that were expected due to the condition being treated.
Measured: 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)
Progression Free Survival (PFS): Dose Escalation Phase
PFS was defined as time from date of first study treatment intake to date of first documented disease progression (PD) or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of greater than or equal to (>=) 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier method.
Measured: 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)
PFS: Dose Expansion Phase
PFS was defined as time from date of first study treatment intake to date of first documented PD or death due to any cause. If a participant did not have an event, data censoring was done at the date of last adequate tumor assessment. PD was defined for target disease as at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study), sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier method.
Measured: 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)
Duration of Response (DOR): Dose Escalation Phase
DOR was defined as the time from first observation of response CR or partial response [PR]) to the first time of progression or death. CR was defined as complete disappearance of all target and non-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. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
Measured: From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)
Time to Response (TTR): Dose Escalation Phase
TTR was defined as the time from date of treatment until first documented response (CR or PR). 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. Individual participant data have been reported for this outcome measure.
Measured: From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)
DOR: Dose Expansion Phase
DOR was defined as the time from first observation of response (CR or PR] to the first time of progression or death. CR was defined as complete disappearance of all target and non-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 (<10 mm. PR defined as at least 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
Measured: 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)
TTR: Dose Expansion Phase
TTR was defined as the time from date of treatment until first documented response (CR or PR). 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. Individual participant data have been reported for this outcome measure.
Measured: 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)
Overall Survival (OS): Dose Expansion Phase
Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
Measured: 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)
Maximum Observed Plasma Concentration of LGX818: Dose Escalation Phase
Measured: 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)
Time Point of Maximum Concentration (Tmax) of LGX818: Dose Escalation Phase
Measured: 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)
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of LGX818: Dose Escalation Phase
AUC (inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Measured: 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)
Area Under the Concentration-Time Curve From Time Zero to Tau (AUCtau) of LGX818: Dose Escalation Phase
Measured: 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)
Elimination Half-life (t1/2) of LGX818: Dose Escalation Phase
t1/2 was the time measured for the plasma concentration to decrease by one half. Terminal phase half-life expressed in hours (hr).
Measured: 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)
Apparent Total Plasma Clearance of Drug (CL/F) of LGX818: Dose Escalation Phase
Measured: 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)
Apparent Volume of Distribution (Vz/F) of LGX818: Dose Escalation Phase
Measured: 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)
Number of Participants According to Tumor Response Per RECIST Criteria- Dose Escalation
Tumor response included: CR, PR, stable disease and disease progression (PD). CR=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=at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
Measured: 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)
Maximum Observed Plasma Concentration of LGX818: Dose Expansion Phase
Measured: 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)
Vz/F of LGX818: Dose Expansion Phase
Measured: 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)
Tmax of LGX818: Dose Expansion Phase
Tmax was the time required to reach the maximum plasma concentration (Cmax). First observed time to reach peak analyte concentration obtained directly from the experimental data without interpolation, expressed in hours (hr).
Measured: 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)
AUCinf of LGX818: Dose Expansion Phase
AUC (inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Measured: 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)
AUCtau of LGX818: Dose Expansion Phase
Measured: 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)
t1/2 of LGX818: Dose Expansion Phase
Measured: 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)
CL/F of LGX818: Dose Expansion Phase
Measured: 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)
Number of Participants According to BRAF V600 Mutation Status at Baseline: Dose Expansion
Number of participants according to BRAF V600 mutation status as V600E (i.e., mutation of the BRAF gene in which valine [V] was substituted by glutamic acid [E] at amino acid 600) or other is reported in this outcome measure.
Measured: (Baseline) last non-missing value prior to the first dose (Baseline)
Number of Participants According to Tumor Response Per RECIST Criteria: Dose Expansion
umor response included: CR, PR, stable disease and disease progression (PD). CR=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=at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease=neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. For target disease, PD=at least a 20% increase in sum of longest diameters of all measured target lesions, taking as reference smallest sum on study, sum also demonstrated absolute increase of >= 5 mm, or appearance of >=1 new lesions. For non-target disease: PD=unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2011 (estimated)
- Study start5 Sep 2011
- Primary completion1 Oct 2012
- Study completion7 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Melanoma and Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01436656
- Sponsor's protocol ID
- CLGX818X2101
- Other IDs
- C4221010, 2011-000556-42
- Status last verified
- Aug 2024
- First submitted
- 14 Apr 2011
- Last updated
- 28 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated device
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01436656
- Acronym / sponsor ID
- CLGX818X2101
- Keywords
- BRAF mutant,, BRAF mutated,, melanoma,, metastatic,, advanced,, RAF kinase inhibitor, BRAF V600 mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2011 (actual)
- Primary completion
- 1 Oct 2012 (actual)
- Study completion
- 7 Nov 2022 (actual)
- First posted
- 20 Sep 2011 (estimated)
- Results
- Posted 28 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LGX818 - Dose escalation | Experimental | Drug: LGX818 |
| LGX818 - Dose Expansion at MTD or RP2D | Experimental | Drug: LGX818 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LGX818 | Drug | LGX818 - Dose Expansion at MTD or RP2D, LGX818 - Dose escalation |
Primary outcome
Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase
Time frame: Up to 28 days
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
Number of Participants With DLT During Dose Expansion Phase
Time frame: Up to 28 days
DLT= Adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within first 28 days of treatment with encorafenib and met any of following criteria: >=grade (G)3 neutropenia or thrombocytopenia for >7 days; G4 thrombocytopenia; febrile neutropenia; >=G3 serum creatinine, blood bilirubin; alanine aminotransferase (ALT) or aspartate aminotransferase (AST) and lipase and/or serum amylase (>=G3 for > 7 consecutive days or G4); >=G3 ALT or AST and >=G2 blood bilirubin; >=G3 persistent hypertension with more than one drug or more intensive therapy or cardiac disorders or AE excluding on-target side-effect that is manageable; G3 fatigue/asthenia for >7 consecutive days; >= G3 vomiting or nausea or diarrhea lasting more than 48 hours despite treatment; >=G3 pancreatitis, rash/photosensitivity (G3 for > 7 consecutive days despite skin toxicity treatment or G4); G3 or G4 eye disorders.
26 secondary outcomes
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) During Dose Escalation Phase
Time frame: From start of study treatment until 30 days after last dose of study treatment (maximum of 556.1 weeks of treatment exposure)
Number of Participants With AEs and SAEs During Dose Expansion Phase
Time frame: 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)
Progression Free Survival (PFS): Dose Escalation Phase
Time frame: 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)
PFS: Dose Expansion Phase
Time frame: 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)
Duration of Response (DOR): Dose Escalation Phase
Time frame: From first observation of response until first time of PD or death due to any cause (Maximum of 556.1 weeks of treatment exposure)
Time to Response (TTR): Dose Escalation Phase
Time frame: From date of start of treatment until CR or PR or censoring date (maximum of 556.1 weeks of treatment exposure)
DOR: Dose Expansion Phase
Time frame: 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)
TTR: Dose Expansion Phase
Time frame: 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)
Overall Survival (OS): Dose Expansion Phase
Time frame: 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)
Maximum Observed Plasma Concentration of LGX818: Dose Escalation Phase
Time frame: 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)
Time Point of Maximum Concentration (Tmax) of LGX818: Dose Escalation Phase
Time frame: 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)
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of LGX818: Dose Escalation Phase
Time frame: 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)
Area Under the Concentration-Time Curve From Time Zero to Tau (AUCtau) of LGX818: Dose Escalation Phase
Time frame: 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)
Elimination Half-life (t1/2) of LGX818: Dose Escalation Phase
Time frame: 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)
Apparent Total Plasma Clearance of Drug (CL/F) of LGX818: Dose Escalation Phase
Time frame: 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)
Apparent Volume of Distribution (Vz/F) of LGX818: Dose Escalation Phase
Time frame: 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)
Number of Participants According to Tumor Response Per RECIST Criteria- Dose Escalation
Time frame: 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)
Maximum Observed Plasma Concentration of LGX818: Dose Expansion Phase
Time frame: 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)
Vz/F of LGX818: Dose Expansion Phase
Time frame: 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)
Tmax of LGX818: Dose Expansion Phase
Time frame: 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)
AUCinf of LGX818: Dose Expansion Phase
Time frame: 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)
AUCtau of LGX818: Dose Expansion Phase
Time frame: 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)
t1/2 of LGX818: Dose Expansion Phase
Time frame: 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)
CL/F of LGX818: Dose Expansion Phase
Time frame: 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)
Number of Participants According to BRAF V600 Mutation Status at Baseline: Dose Expansion
Time frame: (Baseline) last non-missing value prior to the first dose (Baseline)
Number of Participants According to Tumor Response Per RECIST Criteria: Dose Expansion
Time frame: 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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
24 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LGX818 in people with Melanoma and Metastatic Colorectal Cancer, run by Pfizer at 24 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Spain, United States, France, Australia, Switzerland and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose-Limiting Toxicity (DLT) During Dose Escalation Phase (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024.