MEK162 for Patients With RAS/RAF/MEK Activated Tumors

NCT ID: NCT01885195

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-10
• Study Completion Date: 2017-04-11

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

Detailed Description

This is a phase II, open label study to determine the efficacy and safety of treatment with MEK162 in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have activations of the RAS/RAF/MEK pathway and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. This is a signal-seeking study to match patients with mutations in RAF, RAS, NF1 or MEK to the ATP-noncompetitive MEK 1/2 inhibitor, MEK162. Pre-identification of these mutations or activations in the pathway will be performed locally at a CLIA certified laboratory prior to screening for participation on the trial.

Once the patient has been identified, treating physicians who are qualified investigators may contact Novartis to consider enrollment in this study. For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with single agent MEK162. The patient may not receive any additional anti-cancer therapy during treatment with MEK162.

Patients will continue to receive study treatment until disease progression (assessed by RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (per RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML and MM patients). Scans will be assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up.)

Conditions

Solid Tumor and Hematologic Malignancies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT

Study Groups

MEK162

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

Group Type: EXPERIMENTAL

MEK162

Intervention Type: DRUG

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

Interventions

MEK162

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

University of South Alabama / Mitchell Cancer Institute Univ South Alabama

Mobile, Alabama, United States

Alaska Oncology and Hematology AOH (2)

Anchorage, Alaska, United States

Arizona Oncology Associates AZ Oncology Assoc.

Phoenix, Arizona, United States

Arizona Oncology Associates HOPE Division

Phoenix, Arizona, United States

Arizona Oncology Associates PC- NAHOA

Sedona, Arizona, United States

Highlands Oncology Group Highlands Oncology Group (22)

Fayetteville, Arkansas, United States

PCR Oncology

Pismo Beach, California, United States

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

Sacramento, California, United States

Rocky Mountain Cancer Centers USOR

Boulder, Colorado, United States

Yale University School of Medicine Yale Cancer Center

New Haven, Connecticut, United States

Whittingham Cancer Center Norwalk Hospital

Norwalk, Connecticut, United States

Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO

Norwich, Connecticut, United States

Hematology Oncology PC Stamford Hospital

Stamford, Connecticut, United States

Florida Cancer Specialists Florida Cancer Specialists (31

Fort Myers, Florida, United States

Memorial Cancer Institute Memorial Healthcare System

Hollywood, Florida, United States

Cancer Specialists of North Florida

Jacksonville, Florida, United States

Mt. Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Ocala Oncology Center Dept. of Ocala Oncology Center

Ocala, Florida, United States

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

Ocoee, Florida, United States

University Cancer & Blood Center, LLC

Athens, Georgia, United States

Lurie Children's Hospital of Chicago Developmental Therapeutics

Chicago, Illinois, United States

Oncology Specialists, SC Onc Specialists

Park Ridge, Illinois, United States

Illinois Cancer Care IL. Cancer Care

Peoria, Illinois, United States

Indiana University Indiana Univ. - Purdue Univ.

Indianapolis, Indiana, United States

University of Iowa Hospitals & Clinics Regulatory Contact 2

Iowa City, Iowa, United States

Maryland Oncology Hematology, P.A. Oncology Hematology

Rockville, Maryland, United States

Cancer and Hematology Centers of West Michigan Dept. of Oncology

Grand Rapids, Michigan, United States

Metro MN CCOP - Coon Rapids

Coon Rapids, Minnesota, United States

Research Medical Center Research Med Center (2)

Kansas City, Missouri, United States

Washington University School of Medicine Washington University (16)

St Louis, Missouri, United States

Glacier View Research Institute - Cancer Oncology Dept

Kalispell, Montana, United States

Comprehensive Cancer Centers of Nevada CCC of Nevada (21)

Las Vegas, Nevada, United States

Cancer Institute of New Jersey CINJ

New Brunswick, New Jersey, United States

New Mexico Cancer Care Alliance Oncology Dept

Albuquerque, New Mexico, United States

New York Oncology Hematology, P.C. NYOH Latham

Troy, New York, United States

University of North Carolina Chapel Hill Physician Office Building

Chapel Hill, North Carolina, United States

Duke University Medical Center Seeley G. Mudd Bldg.

Durham, North Carolina, United States

Sanford Research/USD-Fargo Sanford Hematology Oncology

Fargo, North Dakota, United States

Cleveland Clinic Foundation Cleveland Clinic (19)

Cleveland, Ohio, United States

Ohio State University Medical Center Comprehensive Cancer Center

Columbus, Ohio, United States

St. Charles Cancer Center

Bend, Oregon, United States

Willamette Valley Clinical Studies Cancer Institute & Res. Ctr.

Eugene, Oregon, United States

Northwest Cancer Specialists Vancouver Cancer Center

Portland, Oregon, United States

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

Portland, Oregon, United States

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

Bethlehem, Pennsylvania, United States

West Penn Allegheny Oncology Network

Natrona Heights, Pennsylvania, United States

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

Willow Grove, Pennsylvania, United States

Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology

Chattanooga, Tennessee, United States

The West Clinic Dept. of the West Clinic

Memphis, Tennessee, United States

Sarah Cannon Research Institute Sarah Cannon Research Inst (51

Nashville, Tennessee, United States

Texas Oncology Presbyterian Hospital (3)

Dallas, Texas, United States

Texas Oncology Texas Oncology - Denton

Dallas, Texas, United States

Texas Oncology Austin Midtown

Dallas, Texas, United States

Texas Oncology Texas Oncology - Midland

Dallas, Texas, United States

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

Dallas, Texas, United States

Oncology Consultants Oncology Group

Houston, Texas, United States

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

Houston, Texas, United States

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

San Antonio, Texas, United States

Tyler Cancer Center Dept.ofTylerCancerCtr. (2)

Tyler, Texas, United States

Deke Slayton Cancer Center Deke Slayton Cancer Center (2)

Webster, Texas, United States

Intermountain Medical Center Intermountain Healthcare

Murray, Utah, United States

Virginia Cancer Specialists, PC Virginia Cancer Specialists

Fairfax, Virginia, United States

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

Reston, Virginia, United States

Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc

Kennewick, Washington, United States

Providence Regional Cancer System

Lacey, Washington, United States

MultiCare Health System Institute for Research & Innovation MultiCare

Tacoma, Washington, United States

Northwest Medical Specialties NW Medical Specialties

Tacoma, Washington, United States

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 30181415 (View on PubMed)

Other Identifiers

C4211007

Identifier Type: OTHER

Identifier Source: secondary_id

CMEK162AUS11

Identifier Type: -

Identifier Source: org_study_id