Clinical trial NCT01885195: MEK162 for Patients With RAS/RAF/MEK Activated Tumors
Official title: Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 3 - MEK162 for Patients With RAS/RAF/MEK Activated Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-06-24
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.)

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

Primary outcomes:
measure: Clinical Benefit Rate (CBR) for Solid Tumors at Week 16 as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Week 16
measure: CBR for Hematologic Tumors at Week 16: Multiple Myeloma
timeFrame: Week 16
measure: CBR for Hematologic Tumors at Week 16: Acute Myeloid Leukemia
timeFrame: Week 16
Secondary outcomes:
measure: Overall Response Rate (ORR) as Per RECIST Version 1.1
timeFrame: From the start of the treatment until disease progression (maximum up to 19.4 months)
measure: ORR for Hematologic Tumors: Multiple Myeloma
timeFrame: From the start of the treatment until disease progression (maximum up to 19.4 months)
measure: ORR for Hematologic Tumors: Acute Myeloid Leukemia
timeFrame: From the start of the treatment until disease progression (maximum up to 19.4 months)
measure: Progression-free Survival (PFS) as Per RECIST Version 1.1
timeFrame: From the date of first dose to the date of the first documented PD, censored date or death (maximum up to 19.4 months)
measure: Overall Survival (OS)
timeFrame: From the date of first dose to the date of death due to any cause (maximum up to 19.4 months)
measure: Duration of Response (DOR) as Per RECIST Version 1.1
timeFrame: From the first documented response (CR or PR) to the date of the first documented PD or death (maximum up to 19.4 months)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
measure: Number of Participants With Vital Sign Abnormality of Greater Than or Equal to (>=) Grade 3 as Per CTCAE v4.03
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
measure: Number of Participants With Shift From Baseline in Clinical Laboratory - Hematology Parameters
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
measure: Number of Participants With Shift From Baseline in Clinical Laboratory - Biochemistry Parameters
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
measure: Number of Participants With Shift From Baseline in Cardiac Imaging
timeFrame: From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: University of South Alabama / Mitchell Cancer Institute Univ South Alabama
state: Alabama
city: Anchorage
country: United States
facility: Alaska Oncology and Hematology AOH (2)
state: Alaska
city: Phoenix
country: United States
facility: Arizona Oncology Associates AZ Oncology Assoc.
state: Arizona
city: Phoenix
country: United States
facility: Arizona Oncology Associates HOPE Division
state: Arizona
city: Sedona
country: United States
facility: Arizona Oncology Associates PC- NAHOA
state: Arizona
city: Fayetteville
country: United States
facility: Highlands Oncology Group Highlands Oncology Group (22)
state: Arkansas
city: Pismo Beach
country: United States
facility: PCR Oncology
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center UC Davis Cancer (3)
state: California
city: Boulder
country: United States
facility: Rocky Mountain Cancer Centers USOR
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine Yale Cancer Center
state: Connecticut
city: Norwalk
country: United States
facility: Whittingham Cancer Center Norwalk Hospital
state: Connecticut
city: Norwich
country: United States
facility: Eastern Connecticut Hematology & Oncology Associates Dept. of ECHO
state: Connecticut
city: Stamford
country: United States
facility: Hematology Oncology PC Stamford Hospital
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Florida Cancer Specialists (31
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute Memorial Healthcare System
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Miami Beach
country: United States
facility: Mt. Sinai Comprehensive Cancer Center
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center Dept. of Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida PA Cancer Centers of FL-Orlando-4
state: Florida
city: Athens
country: United States
facility: University Cancer & Blood Center, LLC
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago Developmental Therapeutics
state: Illinois
city: Park Ridge
country: United States
facility: Oncology Specialists, SC Onc Specialists
state: Illinois
city: Peoria
country: United States
facility: Illinois Cancer Care IL. Cancer Care
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Indiana Univ. - Purdue Univ.
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals & Clinics Regulatory Contact 2
state: Iowa
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A. Oncology Hematology
state: Maryland
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of West Michigan Dept. of Oncology
state: Michigan
city: Coon Rapids
country: United States
facility: Metro MN CCOP - Coon Rapids
state: Minnesota
city: Kansas City
country: United States
facility: Research Medical Center Research Med Center (2)
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine Washington University (16)
state: Missouri
city: Kalispell
country: United States
facility: Glacier View Research Institute - Cancer Oncology Dept
state: Montana
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada (21)
state: Nevada
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey CINJ
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance Oncology Dept
state: New Mexico
city: Troy
country: United States
facility: New York Oncology Hematology, P.C. NYOH Latham
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Chapel Hill Physician Office Building
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center Seeley G. Mudd Bldg.
state: North Carolina
city: Fargo
country: United States
facility: Sanford Research/USD-Fargo Sanford Hematology Oncology
state: North Dakota
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Cleveland Clinic (19)
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center Comprehensive Cancer Center
state: Ohio
city: Bend
country: United States
facility: St. Charles Cancer Center
state: Oregon
city: Eugene
country: United States
facility: Willamette Valley Clinical Studies Cancer Institute & Res. Ctr.
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists Vancouver Cancer Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University Oregon Health & Science U (56)
state: Oregon
city: Bethlehem
country: United States
facility: St. Luke's Hospital and Health Network St Luke's (2)
state: Pennsylvania
city: Natrona Heights
country: United States
facility: West Penn Allegheny Oncology Network
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Hematology Oncology Associates, Inc Abington Hem Onc Assoc (5)
state: Pennsylvania
city: Chattanooga
country: United States
facility: Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
state: Tennessee
city: Memphis
country: United States
facility: The West Clinic Dept. of the West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Sarah Cannon Research Inst (51
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology Presbyterian Hospital (3)
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Denton
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology Texas Oncology - Midland
state: Texas
city: Dallas
country: United States
facility: Sammons Cancer Center - Texas Oncology Sammons Cancer Center (10)
state: Texas
city: Houston
country: United States
facility: Oncology Consultants Oncology Group
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas / HOAST CCC of So. TX-San Antonio (3)
state: Texas
city: Tyler
country: United States
facility: Tyler Cancer Center Dept.ofTylerCancerCtr. (2)
state: Texas
city: Webster
country: United States
facility: Deke Slayton Cancer Center Deke Slayton Cancer Center (2)
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center Intermountain Healthcare
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC Virginia Cancer Specialists
state: Virginia
city: Reston
country: United States
facility: Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA
state: Virginia
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
state: Washington
city: Lacey
country: United States
facility: Providence Regional Cancer System
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research & Innovation MultiCare
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties NW Medical Specialties
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.