Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 4 - LGX818 for Patients With BRAFV600 Mutated Tumors
Overview
- Phase
- Phase 2
- Intervention
- LGX818
- Conditions
- Solid Tumor
- Sponsor
- Pfizer
- Enrollment
- 12
- Locations
- 13
- Primary Endpoint
- Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- Status
- Terminated
- Last Updated
- 5 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- •Patient has received prior treatment with LGX
- •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.
Arms & Interventions
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.
Intervention: LGX818
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1(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(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(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(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(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(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(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(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(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(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(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(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(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))