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A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

Primary Purpose

BRAF or NRAS Mutant Metastatic Melanoma

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

MEK162

About this trial

This is an interventional treatment trial for BRAF or NRAS Mutant Metastatic Melanoma focused on measuring Metastatic melanoma,, BRAF-mutant,, NRAS-mutant

Eligibility Criteria

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

Inclusion Criteria:

Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery
BRAF or NRAS mutation in tumor tissue
All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol
Evidence of measurable tumor disease as per RECIST
WHO performance status of 0-2
Adequate organ function and laboratory parameters

Exclusion Criteria:

History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO
Patients with unstable CNS metastasis
Prior treatment with a MEK- inhibitor
Impaired cardiovascular function
HIV, active Hepatitis B, and/or active Hepatitis C infection
Pregnant or nursing (lactating) women
Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

Highlands Oncology Group
H. Lee Moffitt Cancer Center & Research Institute, Inc.
OHSU Knight Cancer Institute
OHSU Center for Health and Healing
Oregon Health and Science University
Cancer Care Associates Medical Oncology
St. Luke's Cancer Center - Allentown Campus
Cancer Care Associates Medical Oncology
St. Luke's University Health Network
St. Luke's Hospital - Quakertown Campus
LMU Klinikum der Universität
LMU Klinikum der Universität München
Universitätsklinikum Essen
Universitatsklinikum Schleswig-Holstein
Universitatsklinikum Schleswig-Holstein
Universitatsklinikum Schleswig-Holstein
SRH Wald-Klinikum Gera GmbH
LMU Klinikum der Universität München
Istituto nazionale Per la Ricerca sul Cancro
Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
Radboud University Nijmegen Medical Centre
Maastricht University Medical Center
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
Slotervaartziekenhuis
Universitätsspital Zürich

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

BRAFV600 mutant, 45mg bid MEK162

NRAS mutant, 45mg bid MEK162

BRAFV600 mutant, 60mg bid MEK162

Arm Description

BRAFV600 mutant, 45mg bid MEK162

NRAS mutant, 45mg bid MEK162

BRAFV600 mutant, 60mg bid MEK162

Outcomes

Primary Outcome Measures

Percentage of Participants With Objective Response (OR)

Objective response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.0, was defined as 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-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.

Secondary Outcome Measures

Progression-Free Survival (PFS)

PFS as assessed by investigator per RECIST v1.0, was defined as time (in months) from date of randomization or date of start of treatment to first documentation of PD or date of death due to any cause or data censoring date, whichever occurred first. 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. If a participant did not had an event, data censoring was done at the date of last adequate tumor assessment. Analysis was performed using Kaplan-Meier method.

Overall Survival (OS)

Overall survival 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.

Duration of Response (DOR)

DOR:time from first documentation of OR(confirmed CR or PR) to first documentation of PD/death due to any cause/data censoring date,whichever occurred first. As per RECIST v1.0, CR:disappearance of all target(T) and non-target(Non-T) lesions sustained for =>4 weeks. Any pathological lymph nodes(T or non-T) reduced in short axis to <10mm. PR:>=30% decrease in sum of diameters(SOD) of T lesions, taking as reference baseline SOD. PD for T lesions:at least a 20% increase in sum of diameters of T lesions, taking as reference smallest sum on study treatment, with absolute increase of >=5 mm, or appearance of >=1 new lesions.PD for Non-T lesions:unequivocal progression of pre-existing lesions/increase in overall tumor burden leading to discontinuation of therapy/appearance of new unequivocal malignant lesion.Data was censored on date of last adequate tumor assessment for participants without an event,who started new anti-cancer treatment prior to assessment,who missed >=2 tumor assessments.

Time to Response (TTR)

TTR as assessed by investigator according to RECIST v1.0, 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.

Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Reactions Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.0

An adverse drug reaction (ADR) 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 ADRs 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 ADR were reported in this outcome measure.

Number of Participants With Serious Adverse Reactions

A serious ADR was an ADR resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly, important medical event.

Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Hematology)

Hematology per NCI-CTCAE included, Lymphocyte count decreased-(G1:<0.8, G2:<0.8-0.5, G3:<0.5-0.2, G4:<0.2[*10^9/L]); Lymphocyte count increased-(G2:>4-20, G3:>20[*10^9/L]); Neutrophil count decreased-(G1:<1.5, G2:<1.5-1.0, G3:<1.0-0.5, G4:<0.5[*10^9/L]); Activated partial thromboplastin time prolonged (seconds)-(G1:>1.5*upper limit normal (ULN), G2:>1.5-2.5*ULN, G3:>2.5*ULN); Platelet count decreased-(G1:<75.0, G2:<75.0-50.0, G3:<50.0-25.0, G4:<25.0[*10^9/L]); Fibrinogen decreased-(G1:<1.0-0.75*lower limit normal (LLN), G2:<0.75-0.5*LLN, G3:<0.5-0.25*LLN G4:<0.25*LLN); Anemia-(G1:<LLN-100, G2:<100-80, G3:<80 [g/L], G4:Life-threatening, G5:death); Hemoglobin increased-(G1:>0-2 g/dL above ULN, G2:>2-4 g/dL above ULN, G3:>4 g/dL above ULN); Prothrombin time (INR) increased-(G1:>1-1.5, G2:>1.5-2.5, G3:>2.5[*ULN]); WBC decreased-(G1:<3.0*10^9/L, G2:<3.0-2.0*10^9/L, G3:<2.0-1.0*10^9/L, G4:<1.0*10^9/L); WBC increased-(G3:>100,000/mm3, G4:Clinical manifestations of increase in WBC, G5:death).

Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Chemistries)

Albumin(G1:<30,G2:<30-20,G3:<20[g/L], G4:life-threatening, G5:death);Alkaline phosphatase(G1:>2.5,G2:>2.5-5.0,G3:>5.0-20.0, G4:>20.0[*ULN]);Creatine kinase(G1:>2.5,G2:>2.5-5,G3:>5-10,G4:>10[*ULN]);Creatinine(CT) clearance(G1:<LLN-60,G2:59-30,G3:29-15,G3:<15[ml/min/1.73m^2], G5:death);CT (G1:>1.5,G2:>1.5-3.0,G3:>3.0-6.0,G4:>6.0[*ULN]);Hypomagnesemia(G1:<0.5,G2:<0.5-0.4,G3:<0.4-0.3,G4:<0.3[mmol/L],G5:death);Hypermagnesemia(G1:>1.23,G3:>1.23-3.30, G4:>3.30[mmol/L],G5:death);Hypophosphatemia(G1:<0.8,G2:<0.8-0.6,G3:<0.6-0.3,G4:<0.3[mmol/L], G5:death);Hypokalemia(G1:<3.0,G2:<3.0,G3:<3.0-2.5,G4:<2.5[mmol/L],G5:death);Hyperkalemia(G1:>5.5,G2:>5.5-6.0,G3:>6.0-7.0, G4:>7.0[mmol/L],G5:death);AST(G1:>3.0,G2:>3.0-5.0,G3:>5.0-20.0,G4:>20.0[*ULN]); ALT(G1:>3.0,G2:>3.0-5.0,G3:>5.0-20.0,G4:>20.0[*ULN]);Hyponatremia(G1:<130,G3:<130-120,G4:<120[mmol/L],G5:death);Hypernatremia(G1:150,G2:>150-155,G3:>155-160,G4:>160[mmol/L],G5:death);High blood bilirubin (G1:>1.5,G2:>1.5-3.0,G3:>3.0-10.0,G4:>10.0[*ULN]).

Number of Participants With Shift From Baseline in Vital Signs Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Blood Pressure)

Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP).

Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate

Pre-defined criteria of markedly abnormal vital signs abnormalities was defined as increase or decrease from baseline (>=15 beats per minute) in pulse rate of >=120 beats per minute or less than or equal to (<=) 50 beats per minute.

Number of Participants With Markedly Abnormal Vital Sign Values: Weight

Vital signs included assessment of body weight. Body weight (in kilograms) measurements included high and low. Pre-defined criteria of markedly abnormal vital signs abnormalities was defined as increase or decrease from baseline in weight of >=10%.

Number of Participants With Notable Electrocardiogram (ECG) Values

ECG findings included maximum value of >450 millisecond (msec), >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval corrected using Fridericia's formula (QTcF); maximum value of >450 msec, >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval corrected using Bazett's formula (QTcB); maximum value of >450 msec, >480 msec and >500 msec, increase from baseline >30 msec and >60 msec for QT interval; RR decrease >25% and to a VR >100, RR increase >25% and to a VR <50 beats per minute for VR interval; an increase >25% and to a value >200 msec for PR interval; an increase >25% and to a value >110 msec for QRS interval.

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy

Fundoscopy examination included an examination of the retina, vitreous, macula, optic nerve, optic nerve pallor, choroid and other new abnormalities in either or both eyes. New abnormalities were identified where the baseline assessment showed no abnormalities in a particular eye, but at the post-dose time point an abnormality was observed. New abnormalities at any time point were reported and included unscheduled assessments.

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination

Slit lamp examination included an examination of the conjunctiva, cornea, iris, lens, anterior chamber, lids and other new abnormalities in either or both eyes. New abnormalities were identified where the baseline assessment showed no abnormalities in a particular eye, but at the post-dose time point an abnormality was observed. New abnormalities at any time point were reported and included unscheduled assessments.

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib

Maximum Plasma Concentration (Cmax) of Binimetinib

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib

Trough Plasma Concentration (Ctrough) of Binimetinib

Ctrough refers to plasma concentration of Binimetinib observed just before treatment administration.

Apparent Total Body Clearance (CL/F) of Binimetinib

Drug clearance was defined as a quantitative measure of the rate at which a drug substance was removed from the plasma. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite

Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite

Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite

Ctrough refers to plasma concentration of Binimetinib's metabolite observed just before treatment administration.

Percent Change From Baseline in Histological Score (H-score) for Phosphorylated Extracellular Signal-Regulated Kinase (pERK) From Tumor Samples of Cytoplasmic and Nuclear Cellular Compartment

Percent change from baseline in H-score for pERK from tumor samples was assessed and summarized. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.

Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples

The percentage change in DUSP6 gene expression was derived from the Relative Expression Ratio (RER) computed via the Delta Ct method. DUSP6, a protein coding gene was used as a biomarker of inhibition of the mitogen-activated protein kinase (MEK) pathway.

Full Information

NCT ID

NCT01320085

First Posted

March 14, 2011

Last Updated

August 1, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01320085

Brief Title

A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

Official Title

A Phase II, Open-label Study to Assess the Safety and Efficacy of Oral MEK162 in Adults With Locally Advanced and Unresectable or Metastatic Malignant Cutaneous Melanoma, Harboring BRAFV600 or NRAS Mutations

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Completed

Study Start Date

March 24, 2011 (Actual)

Primary Completion Date

January 7, 2014 (Actual)

Study Completion Date

February 6, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

5. Study Description

Brief Summary

The study will assess the safety and efficacy of single-agent MEK162 in adult patients with locally advanced and unresectable or metastatic malignant cutaneous melanoma, harboring BRAFV600E or NRAS mutations.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

BRAF or NRAS Mutant Metastatic Melanoma

Keywords

Metastatic melanoma,, BRAF-mutant,, NRAS-mutant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

183 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BRAFV600 mutant, 45mg bid MEK162

Arm Type

Experimental

Arm Description

BRAFV600 mutant, 45mg bid MEK162

Arm Title

NRAS mutant, 45mg bid MEK162

Arm Type

Experimental

Arm Description

NRAS mutant, 45mg bid MEK162

Arm Title

BRAFV600 mutant, 60mg bid MEK162

Arm Type

Experimental

Arm Description

BRAFV600 mutant, 60mg bid MEK162

Intervention Type

Drug

Intervention Name(s)

MEK162

Primary Outcome Measure Information:

Title

Percentage of Participants With Objective Response (OR)

Description

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, whichever occurred first (maximum duration of up to 33 months)

Secondary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time Frame

From date of randomization or date of start of treatment until date of first documentation of PD or date of death due to any cause or date of data censoring, whichever occurred first (maximum duration of up to 33 months)

Title

Overall Survival (OS)

Description

Time Frame

From date of randomization or date of start of treatment to date of death due to any cause or date of censoring, whichever occurred first (maximum duration of up to 33 months)

Title

Duration of Response (DOR)

Description

Time Frame

From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum duration of up to 33 months)

Title

Time to Response (TTR)

Description

Time Frame

From the date of randomization or date of start of treatment to the first documentation of objective response (CR or PR) or data censoring date, whichever occurred first (maximum duration of up to 33 months)

Title

Number of Participants With Grade 3 or 4 Treatment-Emergent Adverse Reactions Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.0

Description

Time Frame

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

Title

Number of Participants With Serious Adverse Reactions

Description

Time Frame

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

Title

Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Hematology)

Description

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Chemistries)

Description

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Shift From Baseline in Vital Signs Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0 (Blood Pressure)

Description

Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP).

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate

Description

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Markedly Abnormal Vital Sign Values: Weight

Description

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Notable Electrocardiogram (ECG) Values

Description

Time Frame

Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)

Title

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy

Description

Time Frame

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

Title

Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination

Description

Time Frame

Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)

Title

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Maximum Plasma Concentration (Cmax) of Binimetinib

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Trough Plasma Concentration (Ctrough) of Binimetinib

Description

Ctrough refers to plasma concentration of Binimetinib observed just before treatment administration.

Time Frame

Pre-dose (0 hour) on Day 15 of Cycle 1

Title

Apparent Total Body Clearance (CL/F) of Binimetinib

Description

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite

Time Frame

Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1

Title

Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite

Description

Ctrough refers to plasma concentration of Binimetinib's metabolite observed just before treatment administration.

Time Frame

Pre-dose (0 hour) on Day 15 of Cycle 1

Title

Percent Change From Baseline in Histological Score (H-score) for Phosphorylated Extracellular Signal-Regulated Kinase (pERK) From Tumor Samples of Cytoplasmic and Nuclear Cellular Compartment

Description

Time Frame

Baseline up to maximum duration of up to 33 months

Title

Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples

Description

Time Frame

Baseline up to maximum duration of up to 33 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Locally advanced or metastatic cutaneous melanoma AJCC Stage IIIB to IV, not potentially curable with surgery BRAF or NRAS mutation in tumor tissue All patients enrolled should provide sufficient fresh or archival tumor sample at baseline to enable confirmation of BRAF or NRAS mutations and the additional analyses described in the protocol Evidence of measurable tumor disease as per RECIST WHO performance status of 0-2 Adequate organ function and laboratory parameters Exclusion Criteria: History or evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for CSR or RVO Patients with unstable CNS metastasis Prior treatment with a MEK- inhibitor Impaired cardiovascular function HIV, active Hepatitis B, and/or active Hepatitis C infection Pregnant or nursing (lactating) women Women of child-bearing potential UNLESS they comply with protocol contraceptive requirements Other protocol-defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Highlands Oncology Group

City

Fayetteville

State/Province

Arkansas

ZIP/Postal Code

72703-4005

Country

United States

Facility Name

H. Lee Moffitt Cancer Center & Research Institute, Inc.

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

OHSU Knight Cancer Institute

City

Portland

State/Province

Oregon

ZIP/Postal Code

97201

Country

United States

Facility Name

OHSU Center for Health and Healing

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Oregon Health and Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

Facility Name

Cancer Care Associates Medical Oncology

City

Allentown

State/Province

Pennsylvania

ZIP/Postal Code

18104

Country

United States

Facility Name

St. Luke's Cancer Center - Allentown Campus

City

Allentown

State/Province

Pennsylvania

ZIP/Postal Code

18104

Country

United States

Facility Name

Cancer Care Associates Medical Oncology

City

Bethlehem

State/Province

Pennsylvania

ZIP/Postal Code

18015

Country

United States

Facility Name

St. Luke's University Health Network

City

Bethlehem

State/Province

Pennsylvania

ZIP/Postal Code

18015

Country

United States

Facility Name

St. Luke's Hospital - Quakertown Campus

City

Quakertown

State/Province

Pennsylvania

ZIP/Postal Code

18951

Country

United States

Facility Name

LMU Klinikum der Universität

City

Muenchen

State/Province

Bayern

ZIP/Postal Code

80337

Country

Germany

Facility Name

LMU Klinikum der Universität München

City

München

State/Province

Bayern

ZIP/Postal Code

80337

Country

Germany

Facility Name

Universitätsklinikum Essen

City

Essen

State/Province

Nordrhein-westfalen

ZIP/Postal Code

45122

Country

Germany

Facility Name

Universitatsklinikum Schleswig-Holstein

City

Kiel

State/Province

Schleswig-holstein

ZIP/Postal Code

24105

Country

Germany

Facility Name

Universitatsklinikum Schleswig-Holstein

City

Kiel

State/Province

Schleswig-holstein

ZIP/Postal Code

D-24105

Country

Germany

Facility Name

Universitatsklinikum Schleswig-Holstein

City

Luebeck

State/Province

Schleswig-holstein

ZIP/Postal Code

23562

Country

Germany

Facility Name

SRH Wald-Klinikum Gera GmbH

City

Gera

State/Province

Thüringen

ZIP/Postal Code

07548

Country

Germany

Facility Name

LMU Klinikum der Universität München

City

Munich

ZIP/Postal Code

80337

Country

Germany

Facility Name

Istituto nazionale Per la Ricerca sul Cancro

City

Genova

ZIP/Postal Code

16132

Country

Italy

Facility Name

Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale

City

Napoli

ZIP/Postal Code

80131

Country

Italy

Facility Name

Radboud University Nijmegen Medical Centre

City

Nijmegen

State/Province

Gelderland

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Maastricht University Medical Center

City

Maastricht

State/Province

Limburg

ZIP/Postal Code

6229 HX

Country

Netherlands

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

Slotervaartziekenhuis

City

Amsterdam

State/Province

Noord-holland

ZIP/Postal Code

1066 EC

Country

Netherlands

Facility Name

Universitätsspital Zürich

City

Zürich (de)

ZIP/Postal Code

08091

Country

Switzerland

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

Citations:

PubMed Identifier

23414587

Citation

Ascierto PA, Schadendorf D, Berking C, Agarwala SS, van Herpen CM, Queirolo P, Blank CU, Hauschild A, Beck JT, St-Pierre A, Niazi F, Wandel S, Peters M, Zubel A, Dummer R. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study. Lancet Oncol. 2013 Mar;14(3):249-56. doi: 10.1016/S1470-2045(13)70024-X. Epub 2013 Feb 13.

Results Reference

derived

Learn more about this trial

A Phase II Study of Single Agent MEK162 in Patients With Advanced Melanoma

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