Clinical trial NCT01320085: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: BRAF or NRAS Mutant Metastatic Melanoma
Keywords: Metastatic melanoma,
BRAF-mutant,
NRAS-mutant
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-03-22
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Percentage of Participants With Objective Response (OR)
timeFrame: 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 outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: Duration of Response (DOR)
timeFrame: 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)
measure: Time to Response (TTR)
timeFrame: 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)
measure: 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
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)
measure: Number of Participants With Serious Adverse Reactions
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)
measure: 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)
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)
measure: 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)
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 11 years, approximately)
measure: 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)
timeFrame: Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)
measure: Number of Participants With Markedly Abnormal Vital Sign Values: Sitting Pulse Rate
timeFrame: Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)
measure: Number of Participants With Markedly Abnormal Vital Sign Values: Weight
timeFrame: Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)
measure: Number of Participants With Notable Electrocardiogram (ECG) Values
timeFrame: Baseline up to 30 days after last dose of study drug (up to maximum of 33 months)
measure: Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Fundoscopy
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)
measure: Number of Participants With Change From Baseline in Abnormal Ophthalmoscopy Values- by Slit Lamp Examination
timeFrame: Baseline up to 30 days after last dose of study drug (for a maximum duration of up to 33 months)
measure: Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Maximum Plasma Concentration (Cmax) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Trough Plasma Concentration (Ctrough) of Binimetinib
timeFrame: Pre-dose (0 hour) on Day 15 of Cycle 1
measure: Apparent Total Body Clearance (CL/F) of Binimetinib
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Area Under the Curve From Time Zero to End of Dosing Interval at Steady-State (AUCtau) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Maximum Plasma Concentration (Cmax) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration (AUC0-last) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: The Last Time Point of the Last Quantifiable Concentration (Tlast) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour), 0.5, 1.5, 3, 8 hours on Day 1 and Day 15 of Cycle 1
measure: Trough Plasma Concentration (Ctrough) of Binimetinib's Metabolite
timeFrame: Pre-dose (0 hour) on Day 15 of Cycle 1
measure: 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
timeFrame: Baseline up to maximum duration of up to 33 months
measure: Percent Change From Baseline in Delta CT Values for Dual Specificity Phosphatase 6 (DUSP6) Expression From Tumor Samples
timeFrame: Baseline up to maximum duration of up to 33 months
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute, Inc.
state: Florida
city: Portland
country: United States
facility: OHSU Knight Cancer Institute
state: Oregon
city: Portland
country: United States
facility: OHSU Center for Health and Healing
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Allentown
country: United States
facility: Cancer Care Associates Medical Oncology
state: Pennsylvania
city: Allentown
country: United States
facility: St. Luke's Cancer Center - Allentown Campus
state: Pennsylvania
city: Bethlehem
country: United States
facility: Cancer Care Associates Medical Oncology
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Quakertown
country: United States
facility: St. Luke's Hospital - Quakertown Campus
state: Pennsylvania
city: Muenchen
country: Germany
facility: LMU Klinikum der Universität
state: Bayern
city: München
country: Germany
facility: LMU Klinikum der Universität München
state: Bayern
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-westfalen
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-holstein
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-holstein
city: Luebeck
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-holstein
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera GmbH
state: Thüringen
city: Munich
country: Germany
facility: LMU Klinikum der Universität München
city: Genova
country: Italy
facility: Istituto nazionale Per la Ricerca sul Cancro
city: Napoli
country: Italy
facility: Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
state: Limburg
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
state: Noord-holland
city: Amsterdam
country: Netherlands
facility: Slotervaartziekenhuis
state: Noord-holland
city: Zürich (de)
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Pfizer
name: Pfizer Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
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.