LGX818 for Patients With BRAFV600 Mutated Tumors (SIGNATURE)

March 1, 2021 updated by: Pfizer

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 4 - LGX818 for Patients With BRAFV600 Mutated Tumors

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
12

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35211
        • Alabama Oncology St. Vincent's Birmingham
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group Highlands Oncology Group (22)
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale University School Of Medicine Smilow Cancer Hospital
      • Norwalk, Connecticut, United States, 06856
        • Whittingham Cancer Center Norwalk Hospital
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Florida Cancer Specialists Florida Cancer Specialists (31
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Lurie Children's Hospital of Chicago Developmental Therapeutics
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
    • Ohio
      • Zanesville, Ohio, United States, 43701
        • Genesis Cancer Services
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Presbyterian Medical Center University of Pennsylvania
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Research Sanford Health
    • Texas
      • Houston, Texas, United States, 77024
        • Oncology Consultants Oncology Group
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Utah Cancer Specialists Utah Cancer Specialists (11)
    • Virginia
      • Winchester, Virginia, United States, 22601
        • Shenandoah Oncology Shenadoah Oncology (2)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LGX818
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.
Drug: LGX818
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Up to 13.3 months
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.
Up to 13.3 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1
Time Frame: From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)
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.
From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)
Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1
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)
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.
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)
Overall Survival (OS) for Solid Tumors
Time Frame: From date of the first dose until the date of death, censored date (maximum up to 13.3 months)
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.
From date of the first dose until the date of death, censored date (maximum up to 13.3 months)
Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1
Time Frame: From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months)
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.
From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months)
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
Time Frame: Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)
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.
Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)
Change From Baseline in Systolic and Diastolic Blood Pressure
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)
Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.
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)
Change From Baseline in Sitting Pulse Rate
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)
Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.
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)
Change From Baseline in Body Temperature
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)
Change from baseline in body temperature in degree Celsius was reported.
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)
Change From Baseline in Respiratory Rate
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)
Change from baseline in respiratory rate in breaths per minute was reported.
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)
Change From Baseline in Body Weight
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)
Change from baseline in body weight in kilogram (Kg) was reported
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)
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities
Time Frame: Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)
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.
Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration
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)
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.
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)
Change From Baseline in Heart Rate
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)
Change from baseline in heart rate in terms of beats per minute was reported.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 14, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 13, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 5, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 5, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 11, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 26, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLGX818AUS03
  • C4221021 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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