Back to resultsLGX818 for Patients With BRAFV600 Mutated Tumors (SIGNATURE)
Primary Purpose
Solid Tumor, Hematologic Malignancies
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LGX818
Sponsored by
About this trial
This is an interventional treatment trial for Solid Tumor
Eligibility Criteria
Inclusion Criteria
- Patient has a confirmed diagnosis of a select solid tumor (except with a primary diagnosis of melanoma and colorectal cancer (CRC)) or hematologic malignancies and is in need of treatment because of progression or relapse.
- Patient's tumor has been evaluated and pre-identified as having a tumor with a BRAFV600 mutation 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 per RECIST 1.1. or other appropriate hematological response criteria.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Exclusion Criteria:
- Patient has received prior treatment with LGX818.
- Patients with Central Nerve System (CNS) metastasis or leptomeningeal carcinomatosis.
- Patient has received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.
- Patients with acute or chronic pancreatitis.
- Patients with impaired cardiac function or clinically significant cardiac diseases.
- Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix.
Sites / Locations
- Alabama Oncology St. Vincent's Birmingham
- Highlands Oncology Group Highlands Oncology Group (22)
- Yale University School of Medicine Smilow Cancer Hospital
- Whittingham Cancer Center Norwalk Hospital
- Florida Cancer Specialists Florida Cancer Specialists (31
- Lurie Children's Hospital of Chicago Developmental Therapeutics
- Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
- Genesis Cancer Services
- University of Pennsylvania Presbyterian Medical Center University of Pennsylvania
- Sanford Research Sanford Health
- Oncology Consultants Oncology Group
- Utah Cancer Specialists Utah Cancer Specialists (11)
- Shenandoah Oncology Shenadoah Oncology (2)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LGX818
Arm Description
LGX818 will be dosed on a flat scale of 300 mg (e.g., 3 x 100 mg capsules) once daily on a continuous dosing cycle. A complete treatment cycle is defined as 28 days. There will be no breaks between dosing cycles.
Outcomes
Primary Outcome Measures
Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. PD was defined as 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.
Secondary Outcome Measures
Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1
ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1
PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. PD was defined as 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. Participants who had no event were censored at the date of last adequate tumor assessment.
Overall Survival (OS) for Solid Tumors
OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact.
Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1
DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as 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.
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. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study.
Change From Baseline in Systolic and Diastolic Blood Pressure
Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.
Change From Baseline in Sitting Pulse Rate
Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.
Change From Baseline in Body Temperature
Change from baseline in body temperature in degree Celsius was reported.
Change From Baseline in Respiratory Rate
Change from baseline in respiratory rate in breaths per minute was reported.
Change From Baseline in Body Weight
Change from baseline in body weight in kilogram (Kg) was reported
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities
Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration
Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.
Change From Baseline in Heart Rate
Change from baseline in heart rate in terms of beats per minute was reported.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01981187
Brief Title
LGX818 for Patients With BRAFV600 Mutated Tumors
Acronym
SIGNATURE
Official Title
Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 4 - LGX818 for Patients With BRAFV600 Mutated Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Due to slow enrollment and lack of response observed during the enrollment period, the Sponsor decided to close study enrollment early on 28 January 2015
Study Start Date
January 14, 2014 (Actual)
Primary Completion Date
September 1, 2015 (Actual)
Study Completion Date
October 13, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this signal seeking study is to determine whether treatment with LGX818 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumor, Hematologic Malignancies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LGX818
Arm Type
Experimental
Arm Description
LGX818 will be dosed on a flat scale of 300 mg (e.g., 3 x 100 mg capsules) once daily on a continuous dosing cycle. A complete treatment cycle is defined as 28 days. There will be no breaks between dosing cycles.
Intervention Type
Drug
Intervention Name(s)
LGX818
Intervention Description
LGX818 will be dosed on a flat scale of 300 mg (e.g., 3 x 100 mg capsules) once daily on a continuous dosing cycle. A complete treatment cycle is defined as 28 days. There will be no breaks between dosing cycles.
Primary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description
CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. PD was defined as 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.
Time Frame
Up to 13.3 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1
Description
ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time Frame
From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)
Title
Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1
Description
PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. PD was defined as 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. Participants who had no event were censored at the date of last adequate tumor assessment.
Time Frame
From the date of first dose until the first documentation of PD, relapse, censored date or death, whichever occurred first (maximum up to 13.3 months)
Title
Overall Survival (OS) for Solid Tumors
Description
OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact.
Time Frame
From date of the first dose until the date of death, censored date (maximum up to 13.3 months)
Title
Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1
Description
DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as 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.
Time Frame
From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months)
Title
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
Description
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. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study.
Time Frame
Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)
Title
Change From Baseline in Systolic and Diastolic Blood Pressure
Description
Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Change From Baseline in Sitting Pulse Rate
Description
Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Change From Baseline in Body Temperature
Description
Change from baseline in body temperature in degree Celsius was reported.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Change From Baseline in Respiratory Rate
Description
Change from baseline in respiratory rate in breaths per minute was reported.
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Change From Baseline in Body Weight
Description
Change from baseline in body weight in kilogram (Kg) was reported
Time Frame
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities
Description
Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal.
Time Frame
Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)
Title
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration
Description
Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.
Time Frame
Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
Title
Change From Baseline in Heart Rate
Description
Change from baseline in heart rate in terms of beats per minute was reported.
Time Frame
Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patient has a confirmed diagnosis of a select solid tumor (except with a primary diagnosis of melanoma and colorectal cancer (CRC)) or hematologic malignancies and is in need of treatment because of progression or relapse.
Patient's tumor has been evaluated and pre-identified as having a tumor with a BRAFV600 mutation 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 per RECIST 1.1. or other appropriate hematological response criteria.
Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
Exclusion Criteria:
Patient has received prior treatment with LGX818.
Patients with Central Nerve System (CNS) metastasis or leptomeningeal carcinomatosis.
Patient has received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.
Patients with acute or chronic pancreatitis.
Patients with impaired cardiac function or clinically significant cardiac diseases.
Patients with another primary malignancy within 3 years prior to starting study treatment, with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Alabama Oncology St. Vincent's Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Facility Name
Highlands Oncology Group Highlands Oncology Group (22)
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72703
Country
United States
Facility Name
Yale University School of Medicine Smilow Cancer Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Whittingham Cancer Center Norwalk Hospital
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856
Country
United States
Facility Name
Florida Cancer Specialists Florida Cancer Specialists (31
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Lurie Children's Hospital of Chicago Developmental Therapeutics
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89109
Country
United States
Facility Name
Genesis Cancer Services
City
Zanesville
State/Province
Ohio
ZIP/Postal Code
43701
Country
United States
Facility Name
University of Pennsylvania Presbyterian Medical Center University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Sanford Research Sanford Health
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57104
Country
United States
Facility Name
Oncology Consultants Oncology Group
City
Houston
State/Province
Texas
ZIP/Postal Code
77024
Country
United States
Facility Name
Utah Cancer Specialists Utah Cancer Specialists (11)
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84106
Country
United States
Facility Name
Shenandoah Oncology Shenadoah Oncology (2)
City
Winchester
State/Province
Virginia
ZIP/Postal Code
22601
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Learn more about this trial
LGX818 for Patients With BRAFV600 Mutated Tumors
We'll reach out to this number within 24 hrs