MEK162 for Patients With RAS/RAF/MEK Activated Tumors

NCT01885195 | Completed Phase 2 Results

• 2 other identifiers: CMEK162AUS11C4211007
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 68

Brief Summary

The purpose of this signal seeking study is to determine whether treatment with MEK162 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study

Conditions

Solid Tumor and Hematologic Malignancies

Keywords

RAS, RAF, MEK, NF1, MEK162, signature, papillary thyroid, small intestine, bladder, esophagus, lung cancer, NSCLC, acute myelogenous leukemia, AML

Outcome Measures

Primary Outcomes (3)

• Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  CBR: participants with complete response (CR), partial response (PR) or stable disease (SD) for at least 16 weeks. As per RECIST 1.1, CR: disappearance of all target and non-target lesions, normalization of tumor marker level, pathological lymph nodes assigned as target or non-target lesions must have a reduction in short axis to less than (\<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters; PD: at least a 20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum was also an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of \>=1 new target or non-target lesions.

  Week 16

• CBR for Hematologic Tumors at Week 16: Multiple Myeloma

  CBR: participants with stringent complete response(sCR), CR, very good partial response(VGPR), PR/SD for at least 16 weeks. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on serum, urine, disappearance of any soft tissue plasmacytomas and \<5% plasma cells in bone marrow plus normal free light chain(FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry/immunofluorescence; CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and \<5% plasma cells in bone marrow; VGPR: serum,urine M-component detectable by immunofixation but not on electrophoresis or\>=90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR: \>50% reduction of serum M-protein and reduction in 24hr urinary M-protein by \>90%/to \<200 mg/24 hr; SD: not meeting criteria for CR, VGPR, PRor PD; PD: increase of \>25% from lowest response value in serum M-component, urine M-component and bone marrow plasma cell percentage.

  Week 16

• CBR for Hematologic Tumors at Week 16: Acute Myeloid Leukemia

  CBR: participants with complete remission (CR), CR with incomplete blood count recovery (CRi), partial remission (PR) and no resposne for at least 16 weeks. For hematologic tumors (acute myeloid leukemia); CR: as bone marrow- \< 5% blasts, no blasts with auer rods, peripheral blood- neutrophils ≥1.0\*10\^9/L and/or platelets ≥100\*10\^9/L, ≤1% blasts, no evidence of extramedullary disease (such as CNS or soft tissue involvement), transfusion independent; CRi: all the CR criteria were involved but platelet and neutrophil transfusions were also allowed; PR: bone marrow- 50% or greater decrease (absolute range 5-25% blasts), \< 5% of blasts contain auer rods, peripheral blood- neutrophils \<1.0\*10\^9/L and/or platelets \<100\*10\^9/L, no evidence of extramedullary disease; no response: in case a patient did not achieve CR, CRi, PR or relapse for an individual response assessment.

  Week 16

Secondary Outcomes (12)

• Overall Response Rate (ORR) as Per RECIST Version 1.1

  From the start of the treatment until disease progression (maximum up to 19.4 months)

• ORR for Hematologic Tumors: Multiple Myeloma

  From the start of the treatment until disease progression (maximum up to 19.4 months)

• ORR for Hematologic Tumors: Acute Myeloid Leukemia

  From the start of the treatment until disease progression (maximum up to 19.4 months)

• Progression-free Survival (PFS) as Per RECIST Version 1.1

  From the date of first dose to the date of the first documented PD, censored date or death (maximum up to 19.4 months)

• Overall Survival (OS)

  From the date of first dose to the date of death due to any cause (maximum up to 19.4 months)

Study Arms (1)

MEK162

EXPERIMENTAL

MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.

Drug: MEK162

Interventions

MEK162 DRUG

MEK162 will be dosed on a flat scale of 45 mg twice daily on a continuous dosing schedule.

MEK162

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a confirmed diagnosis of a select solid tumor (except for primary diagnosis of pancreatic cancer, biliary cancer, colorectal cancer, low grade serous ovarian cancer, melanoma) or hematologic malignancy (except for primary diagnosis of chronic myelomonocytic leukemia).
• Patients must be pre-identified as having a tumor with a mutation in RAF, RAS, NF1 or MEK at a CLIA certified laboratory
• Patient must have received at least one prior treatment for recurrent, metastatic and /or locally advanced disease and for whom no standard therapy options are anticipated to result in a durable remission.
• Patient must have progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

You may not qualify if:

• Patient has received prior treatment with MEK162.
• Patients with primary CNS tumor or CNS tumor involvement
• History of retinal degenerative disease
• History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
• Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist
• Patients who have neuromuscular disorders that are associated with elevated CK

Sponsors & Collaborators

• Pfizer: lead

Study Sites (68)

University of South Alabama / Mitchell Cancer Institute Univ South Alabama

Mobile, Alabama, 36688, United States

Location

Alaska Oncology and Hematology AOH (2)

Anchorage, Alaska, 99508, United States

Location

Arizona Oncology Associates AZ Oncology Assoc.

Phoenix, Arizona, United States

Location

Arizona Oncology Associates HOPE Division

Phoenix, Arizona, United States

Location

Arizona Oncology Associates PC- NAHOA

Sedona, Arizona, 86336, United States

Location

Highlands Oncology Group Highlands Oncology Group (22)

Fayetteville, Arkansas, 72703, United States

Location

PCR Oncology

Pismo Beach, California, 93449, United States

Location

University of California Davis Cancer Center UC Davis Cancer (3)

Sacramento, California, 95817, United States

Location

Rocky Mountain Cancer Centers USOR

Boulder, Colorado, 80304, United States

Location

Yale University School of Medicine Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Whittingham Cancer Center Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO

Norwich, Connecticut, 06360, United States

Location

Hematology Oncology PC Stamford Hospital

Stamford, Connecticut, 06902, United States

Location

Florida Cancer Specialists Florida Cancer Specialists (31

Fort Myers, Florida, 33901, United States

Location

Memorial Cancer Institute Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Cancer Specialists of North Florida

Jacksonville, Florida, 32256, United States

Location

Mt. Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Ocala Oncology Center Dept. of Ocala Oncology Center

Ocala, Florida, 34474, United States

Location

Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4

Ocoee, Florida, United States

Location

University Cancer & Blood Center, LLC

Athens, Georgia, 30607, United States

Location

Lurie Children's Hospital of Chicago Developmental Therapeutics

Chicago, Illinois, 60611, United States

Location

Oncology Specialists, SC Onc Specialists

Park Ridge, Illinois, 60068-0736, United States

Location

Illinois Cancer Care IL. Cancer Care

Peoria, Illinois, 61615-7828, United States

Location

Indiana University Indiana Univ. - Purdue Univ.

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals & Clinics Regulatory Contact 2

Iowa City, Iowa, 52242, United States

Location

Maryland Oncology Hematology, P.A. Oncology Hematology

Rockville, Maryland, 20850, United States

Location

Cancer and Hematology Centers of West Michigan Dept. of Oncology

Grand Rapids, Michigan, 49546, United States

Location

Metro MN CCOP - Coon Rapids

Coon Rapids, Minnesota, 55433, United States

Location

Research Medical Center Research Med Center (2)

Kansas City, Missouri, 64132, United States

Location

Washington University School of Medicine Washington University (16)

St Louis, Missouri, 63110, United States

Location

Glacier View Research Institute - Cancer Oncology Dept

Kalispell, Montana, 59901, United States

Location

Comprehensive Cancer Centers of Nevada CCC of Nevada (21)

Las Vegas, Nevada, 89109, United States

Location

Cancer Institute of New Jersey CINJ

New Brunswick, New Jersey, 08901, United States

Location

New Mexico Cancer Care Alliance Oncology Dept

Albuquerque, New Mexico, 87106, United States

Location

New York Oncology Hematology, P.C. NYOH Latham

Troy, New York, 12180, United States

Location

University of North Carolina Chapel Hill Physician Office Building

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Medical Center Seeley G. Mudd Bldg.

Durham, North Carolina, 27710, United States

Location

Sanford Research/USD-Fargo Sanford Hematology Oncology

Fargo, North Dakota, 58122, United States

Location

Cleveland Clinic Foundation Cleveland Clinic (19)

Cleveland, Ohio, 44195, United States

Location

Ohio State University Medical Center Comprehensive Cancer Center

Columbus, Ohio, 43221, United States

Location

St. Charles Cancer Center

Bend, Oregon, 97701, United States

Location

Willamette Valley Clinical Studies Cancer Institute & Res. Ctr.

Eugene, Oregon, 97404, United States

Location

Northwest Cancer Specialists Vancouver Cancer Center

Portland, Oregon, 97210, United States

Location

Oregon Health & Science University Oregon Health & Science U (56)

Portland, Oregon, 97239, United States

Location

St. Luke's Hospital and Health Network St Luke's (2)

Bethlehem, Pennsylvania, United States

Location

West Penn Allegheny Oncology Network

Natrona Heights, Pennsylvania, 15065, United States

Location

Abington Hematology Oncology Associates, Inc Abington Hem Onc Assoc (5)

Willow Grove, Pennsylvania, 19090, United States

Location

Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

Chattanooga, Tennessee, 37404, United States

Location

The West Clinic Dept. of the West Clinic

Memphis, Tennessee, 38120, United States

Location

Sarah Cannon Research Institute Sarah Cannon Research Inst (51

Nashville, Tennessee, 37203, United States

Location

Texas Oncology Presbyterian Hospital (3)

Dallas, Texas, 75246, United States

Location

Texas Oncology Texas Oncology - Denton

Dallas, Texas, 75246, United States

Location

Texas Oncology Austin Midtown

Dallas, Texas, 75251, United States

Location

Texas Oncology Texas Oncology - Midland

Dallas, Texas, 75251, United States

Location

Sammons Cancer Center - Texas Oncology Sammons Cancer Center (10)

Dallas, Texas, 78246, United States

Location

Oncology Consultants Oncology Group

Houston, Texas, 77024, United States

Location

MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas / HOAST CCC of So. TX-San Antonio (3)

San Antonio, Texas, 78229, United States

Location

Tyler Cancer Center Dept.ofTylerCancerCtr. (2)

Tyler, Texas, 75702, United States

Location

Deke Slayton Cancer Center Deke Slayton Cancer Center (2)

Webster, Texas, 77598, United States

Location

Intermountain Medical Center Intermountain Healthcare

Murray, Utah, 84157, United States

Location

Virginia Cancer Specialists, PC Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA

Reston, Virginia, 20190, United States

Location

Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc

Kennewick, Washington, 99336, United States

Location

Providence Regional Cancer System

Lacey, Washington, 98503, United States

Location

MultiCare Health System Institute for Research & Innovation MultiCare

Tacoma, Washington, 98405, United States

Location

Northwest Medical Specialties NW Medical Specialties

Tacoma, Washington, 98405, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Burkart J, Owen D, Shah MH, Abdel-Misih SRZ, Roychowdhury S, Wesolowski R, Haraldsdottir S, Reeser JW, Samorodnitsky E, Smith A, Konda B. Targeting BRAF Mutations in High-Grade Neuroendocrine Carcinoma of the Colon. J Natl Compr Canc Netw. 2018 Sep;16(9):1035-1040. doi: 10.6004/jnccn.2018.7043.

  PMID: 30181415 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Noonan Syndrome 5; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Leukemia, Myeloid, Acute

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2013
• First Posted: June 24, 2013
• Study Start: October 10, 2013
• Primary Completion: October 1, 2015
• Study Completion: April 11, 2017
• Last Updated: February 21, 2021
• Results First Posted: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share

Locations

US (68)