Solid Tumor and Hematologic Malignancies Clinical Trial
— SIGNATUREOfficial 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
| Verified date | February 2021 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 110 |
| Est. completion date | April 11, 2017 |
| Est. primary completion date | October 1, 2015 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | New Mexico Cancer Care Alliance Oncology Dept | Albuquerque | New Mexico |
| United States | Alaska Oncology and Hematology AOH (2) | Anchorage | Alaska |
| United States | University Cancer & Blood Center, LLC | Athens | Georgia |
| United States | St. Charles Cancer Center | Bend | Oregon |
| United States | St. Luke's Hospital and Health Network St Luke's (2) | Bethlehem | Pennsylvania |
| United States | Rocky Mountain Cancer Centers USOR | Boulder | Colorado |
| United States | University of North Carolina Chapel Hill Physician Office Building | Chapel Hill | North Carolina |
| United States | Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology | Chattanooga | Tennessee |
| United States | Lurie Children's Hospital of Chicago Developmental Therapeutics | Chicago | Illinois |
| United States | Cleveland Clinic Foundation Cleveland Clinic (19) | Cleveland | Ohio |
| United States | Ohio State University Medical Center Comprehensive Cancer Center | Columbus | Ohio |
| United States | Metro MN CCOP - Coon Rapids | Coon Rapids | Minnesota |
| United States | Sammons Cancer Center - Texas Oncology Sammons Cancer Center (10) | Dallas | Texas |
| United States | Texas Oncology Austin Midtown | Dallas | Texas |
| United States | Texas Oncology Presbyterian Hospital (3) | Dallas | Texas |
| United States | Texas Oncology Texas Oncology - Denton | Dallas | Texas |
| United States | Texas Oncology Texas Oncology - Midland | Dallas | Texas |
| United States | Duke University Medical Center Seeley G. Mudd Bldg. | Durham | North Carolina |
| United States | Willamette Valley Clinical Studies Cancer Institute & Res. Ctr. | Eugene | Oregon |
| United States | Virginia Cancer Specialists, PC Virginia Cancer Specialists | Fairfax | Virginia |
| United States | Sanford Research/USD-Fargo Sanford Hematology Oncology | Fargo | North Dakota |
| United States | Highlands Oncology Group Highlands Oncology Group (22) | Fayetteville | Arkansas |
| United States | Florida Cancer Specialists Florida Cancer Specialists (31 | Fort Myers | Florida |
| United States | Cancer and Hematology Centers of West Michigan Dept. of Oncology | Grand Rapids | Michigan |
| United States | Memorial Cancer Institute Memorial Healthcare System | Hollywood | Florida |
| United States | MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3) | Houston | Texas |
| United States | Oncology Consultants Oncology Group | Houston | Texas |
| 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 | Cancer Specialists of North Florida | Jacksonville | Florida |
| United States | Glacier View Research Institute - Cancer Oncology Dept | Kalispell | Montana |
| United States | Research Medical Center Research Med Center (2) | Kansas City | Missouri |
| United States | Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc | Kennewick | Washington |
| United States | Providence Regional Cancer System | Lacey | Washington |
| United States | Comprehensive Cancer Centers of Nevada CCC of Nevada (21) | Las Vegas | Nevada |
| United States | The West Clinic Dept. of the West Clinic | Memphis | Tennessee |
| United States | Mt. Sinai Comprehensive Cancer Center | Miami Beach | Florida |
| United States | Medical College of Wisconsin Cancer Center | Milwaukee | Wisconsin |
| United States | University of South Alabama / Mitchell Cancer Institute Univ South Alabama | Mobile | Alabama |
| United States | Intermountain Medical Center Intermountain Healthcare | Murray | Utah |
| United States | Sarah Cannon Research Institute Sarah Cannon Research Inst (51 | Nashville | Tennessee |
| United States | West Penn Allegheny Oncology Network | Natrona Heights | Pennsylvania |
| United States | Cancer Institute of New Jersey CINJ | New Brunswick | New Jersey |
| 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 | 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 | Oncology Specialists, SC Onc Specialists | Park Ridge | Illinois |
| United States | Illinois Cancer Care IL. Cancer Care | Peoria | Illinois |
| United States | Arizona Oncology Associates AZ Oncology Assoc. | Phoenix | Arizona |
| United States | Arizona Oncology Associates HOPE Division | Phoenix | Arizona |
| United States | PCR Oncology | Pismo Beach | California |
| 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 | Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA | Reston | Virginia |
| United States | Maryland Oncology Hematology, P.A. Oncology Hematology | Rockville | Maryland |
| United States | University of California Davis Cancer Center UC Davis Cancer (3) | Sacramento | California |
| United States | Washington University School of Medicine Washington University (16) | Saint Louis | Missouri |
| United States | Cancer Care Centers of South Texas / HOAST CCC of So. TX-San Antonio (3) | San Antonio | Texas |
| United States | Arizona Oncology Associates PC- NAHOA | Sedona | Arizona |
| United States | Hematology Oncology PC Stamford Hospital | Stamford | Connecticut |
| United States | MultiCare Health System Institute for Research & Innovation MultiCare | Tacoma | Washington |
| United States | Northwest Medical Specialties NW Medical Specialties | Tacoma | Washington |
| United States | New York Oncology Hematology, P.C. NYOH Latham | Troy | New York |
| 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 | Abington Hematology Oncology Associates, Inc Abington Hem Onc Assoc (5) | Willow Grove | Pennsylvania |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | Overall Response Rate (ORR) as Per RECIST Version 1.1 | ORR: percentage of participants with a best overall response (BOR) of CR or PR as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until disease progression (PD). 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 mm; PR: at least a 30 % decrease in sum of diameter of all target lesions, taking as reference the baseline sum of 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. | From the start of the treatment until disease progression (maximum up to 19.4 months) | |
| Secondary | ORR for Hematologic Tumors: Multiple Myeloma | ORR: percentage of participants with sCR, CR, VGPR or PR. For hematologic tumors (multiple myeloma), sCR: negative immunofixation on the serum, urine, disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; CR: CR: negative immunofixation on the serum, urine, disappearance of any soft tissue, plasmacytomas and <5% plasma cells in bone marrow; VGPR: serum and urine M-component detectable by immunofixation but not on electrophoresis or greater than equal to >=90% reduction in serum M-component plus urine M-component <100 mg per 24hour (hr); PR: >50% reduction of serum M-protein and reduction in 24 hr urinary M-protein by >90% or to <200 mg/24 hr. | From the start of the treatment until disease progression (maximum up to 19.4 months) | |
| Secondary | ORR for Hematologic Tumors: Acute Myeloid Leukemia | ORR: 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. | From the start of the treatment until disease progression (maximum up to 19.4 months) | |
| Secondary | Progression-free Survival (PFS) as Per RECIST Version 1.1 | PFS was defined as the time from the date of first dose to the date of first documented PD or relapse or death due to any cause. PD: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of existing non-target lesions. Appearance of >=1 new target or non-target lesions was also considered progression. PFS data was censored at date of last adequate tumor assessment. | From the date of first dose to the date of the first documented PD, censored date or death (maximum up to 19.4 months) | |
| Secondary | Overall Survival (OS) | OS was defined as the time from the date of first dose to the date of death due to any cause. If a participant was not known to have died, survival time was censored at the date of last contact. | From the date of first dose to the date of death due to any cause (maximum up to 19.4 months) | |
| Secondary | Duration of Response (DOR) as Per RECIST Version 1.1 | DOR was defined as the time from the first documented response (CR or PR) to the date of first documented disease progression, relapse or death due to any cause. 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 <10 mm; PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of 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. The DOR was determined only in participants whose best response was PR or greater. | From the first documented response (CR or PR) to the date of the first documented PD or death (maximum up to 19.4 months) | |
| Secondary | 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 | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Treatment-emergent adverse events were defined as new or worsening events that were collected from first study treatment date to last treatment date +30 days. AEs of all grades were reported. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) | |
| Secondary | Number of Participants With Vital Sign Abnormality of Greater Than or Equal to (>=) Grade 3 as Per CTCAE v4.03 | Vital signs included hypertension, hypotension and weight decreased were reported. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. Participants with grade 3 or higher vital sign abnormality are reported. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) | |
| Secondary | Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcF) in millisecond (msec): greater than equal to (>=) 450 to less than (<) 480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60; 2) QTc interval adjusted according to Fridericia formula (QTcB) (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60. 3) QT (msec): >=450 to <480, >=480 to <500, >=500, increase from baseline >=30, increase from baseline >=60. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) | |
| Secondary | Number of Participants With Shift From Baseline in Clinical Laboratory - Hematology Parameters | Laboratory parameters included hematological and biochemistry parameters. Hematological parameters included neutrophils, platelets, prothrombin time, activated partial thromboplastin time, INR, fibrinogen. Number of participants with hematological abnormalities by grades (as per Common Terminology Criteria for Adverse Events (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) | |
| Secondary | Number of Participants With Shift From Baseline in Clinical Laboratory - Biochemistry Parameters | Laboratory parameters included hematological and biochemistry parameters. Biochemistry parameters included: creatinine, phosphorus, albumin, gamma-glutamyl transferase, aspartate transaminase, alanine aminotransferase, alkaline phosphatase, total bilirubin, uric acid, amylase, lipase, creatine kinase, total cholesterol and triglycerides. Number of participants with biochemistry test abnormalities by grades (CTCAE version 4.03) were reported. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Participants with a grade shift of 3 or more from baseline are reported in this outcome measure. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) | |
| Secondary | Number of Participants With Shift From Baseline in Cardiac Imaging | Number of Participants With Shift From Baseline in Cardiac Imaging were reported. | From Baseline up to 30 days following the last dose of study treatment (maximum up to 21 months) |