Clinical trial NCT01981187: LGX818 for Patients With BRAFV600 Mutated Tumors
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solid Tumor
Hematologic Malignancies
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2013-11-11
Enrollment: 12
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 LGX818 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study


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.

Primary outcomes:
measure: Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
timeFrame: Up to 13.3 months
Secondary outcomes:
measure: Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1
timeFrame: From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)
measure: Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1
timeFrame: 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)
measure: Overall Survival (OS) for Solid Tumors
timeFrame: From date of the first dose until the date of death, censored date (maximum up to 13.3 months)
measure: Duration of Response (DOR) for Solid Tumors as Per RECIST Version 1.1
timeFrame: From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 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: Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)
measure: Change From Baseline in Systolic and Diastolic Blood Pressure
timeFrame: 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)
measure: Change From Baseline in Sitting Pulse Rate
timeFrame: 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)
measure: Change From Baseline in Body Temperature
timeFrame: 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)
measure: Change From Baseline in Respiratory Rate
timeFrame: 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)
measure: Change From Baseline in Body Weight
timeFrame: 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)
measure: Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities
timeFrame: Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)
measure: Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration
timeFrame: 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)
measure: Change From Baseline in Heart Rate
timeFrame: 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)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Oncology St. Vincent's Birmingham
state: Alabama
city: Fayetteville
country: United States
facility: Highlands Oncology Group Highlands Oncology Group (22)
state: Arkansas
city: New Haven
country: United States
facility: Yale University School of Medicine Smilow Cancer Hospital
state: Connecticut
city: Norwalk
country: United States
facility: Whittingham Cancer Center Norwalk Hospital
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists Florida Cancer Specialists (31
state: Florida
city: Chicago
country: United States
facility: Lurie Children's Hospital of Chicago Developmental Therapeutics
state: Illinois
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada CCC of Nevada (1)
state: Nevada
city: Zanesville
country: United States
facility: Genesis Cancer Services
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Presbyterian Medical Center University of Pennsylvania
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Research Sanford Health
state: South Dakota
city: Houston
country: United States
facility: Oncology Consultants Oncology Group
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Utah Cancer Specialists (11)
state: Utah
city: Winchester
country: United States
facility: Shenandoah Oncology Shenadoah Oncology (2)
state: Virginia
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: