Brigatinib is a medicine that binds to the surface of tumor cells in some cancers and delivers a dose of chemotherapy directly to the tumor. In this study, participants will be people with non-small-cell lung cancer (NSCLC for short). The main aim of the study is to learn if brigatinib stops the tumors from growing, or if the tumors have shrunk or disappeared, compared to a medicine called alectinib. At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance: * Brigatinib tablets * Alectinib capsules All participants will take brigatinib or alectinib at about the same time every day. They will continue with treatment throughout the study unless their cancer gets worse, they have side effects from the treatment, they leave the study for certain reasons, or the study is stopped. After stopping treatment, participants will visit the study clinic for a check-up 30 days later.
The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to benefit people with anaplastic lymphoma kinase-positive (ALK+) NSCLC. The comparator drug is called alectinib. Alectinib has been demonstrated to benefit people with ALK+ NSCLC. Both drugs belong to a class of drugs called anaplastic lymphoma kinase (ALK) inhibitors. Both drugs are taken by mouth. Both drugs are approved by the United States Food and Drug Administration (US FDA). The study will enroll approximately 246 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups: * Brigatinib * Alectinib All participants will be asked to take brigatinib or alectinib at the same time each day throughout the study. For each participant eligible to continue in the study and to facilitate the remaining participants from Brigatinib-2002 (NCT03535740) to have continued treatment access, the study extension phase may be initiated for participants to continue receiving their randomized study treatment (i.e., brigatinib or alectinib) until they meet at least one of the treatment discontinuation criteria. This multi-center trial will be conducted in the United States, Argentina, Austria, Canada, Chile, China, Croatia, France, Germany, Greece, Hong Kong, Italy, Mexico, Romania, Russia, South Korea, Spain, Sweden, Taiwan, and Thailand. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
248
Brigatinib Tablets.
Alectinib Capsules.
The Oncology Institute of Hope and Innovation
Whittier, California, United States
University Cancer and Blood Center
Athens, Georgia, United States
New York Oncology Hematology - Albany Medical Center
Albany, New York, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Centro Para la Atencion Integral del Paciente Oncologico
San Miguel de Tucumán, Tucumán Province, Argentina
Progression-free Survival (PFS) as Assessed by Blinded Independent Review Committee (BIRC) Per RECIST v1.1
PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1 by BIRC, or death due to any cause, whichever occurs first, in the full analysis set. PFS was censored for participants without documented disease progression or death at the last valid tumor response assessment.
Time frame: Up to 33.8 months
Overall Survival (OS)
OS is defined as the time interval from the date of randomization until death due to any cause in the full analysis set. OS was censored on the date of last contact for those participants who are alive.
Time frame: Up to 64 months
PFS as Assessed by Investigator Per RECIST v1.1
PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1 by investigator, or death due to any cause, whichever occurs first, in the full analysis set. PFS was censored for participants without documented disease progression or death at the last valid tumor response assessment.
Time frame: Up to 33.8 months
Objective Response Rate (ORR) as Assessed by BIRC and Investigator Per RECIST v1.1
ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), using RECIST v1.1 after the initiation of study treatment. Percentages were rounded off to the nearest single decimal place.
Time frame: Up to 33.8 months
Duration of Response (DOR) as Assessed by BIRC and Investigator Per RECIST v1.1
DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease (PD) is objectively documented or death, as assessed by the investigator and BIRC, using RECIST v1.1. Participants who did not progress or died, were censored at the last tumor assessment date prior to receiving subsequent anticancer therapy.
Time frame: Up to 33.8 months
Time to Response as Assessed by Investigator and BIRC Per RECIST v1.1
Time to response is defined as the time interval from randomization until the initial observation of CR or PR, as assessed by the investigator and BIRC, using RECIST v1.1. Time to response will be summarized using descriptive statistics in participants with confirmed objective response.
Time frame: Up to 33.8 months
Confirmed Intracranial Objective Response Rate (iORR) as Assessed by BIRC Per Modified RECIST v1.1
Confirmed iORR, as assessed by the BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) per a modification RECIST v1.1 after the initiation of study treatment in participants with CNS metastases at baseline. Percentages were rounded off to the nearest single decimal place.
Time frame: Up to 33.8 months
Intracranial Duration of Response (iDOR) as Assessed by the BIRC Per Modified RECIST v1.1
iDOR, as assessed by the BIRC per modified RECIST v1.1, is defined as the time interval from the time that the measurement criteria are first met for CR or PR in the CNS (whichever is first recorded) until the first date that the PD in the CNS is objectively documented or death. Participants who did not progress or died, were censored at the last iCNS tumor assessment date prior to receiving subsequent anticancer therapy.
Time frame: Up to 33.8 months
Cumulative Incidence of Intracranial Disease Progression (iPD) as Assessed by BIRC Per Modified RECIST v1.1
Time to iPD as assessed by the BIRC,is defined as time interval from date of randomization until first date at which iPD is objectively documented via a modification of RECIST v1.1 without prior systemic progression (PD) or death. Time to iPD was analyzed within a competing risk framework (with systemic progression and death as the competing risks) by estimating the cumulative incidence function (CIF) within each arm. The CIF is a function of time, and indicates the probability of an event (e.g. iPD without prior PD or death) occurring by the specified time. The estimated CIFs were analyzed using Grey's Test and the estimated probability of CIFs is reported at pre-specified landmark times (6, 12, 18 and 24 months).
Time frame: 6, 12, 18 and 24 months
Health-Related Quality of Life (HRQOL) From European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3.0) Score
EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=Very poor \[worst\] to 7= Excellent \[best\]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL.
Time frame: Up to 33.8 months
HRQOL From EORTC QLQ- Lung Cancer (LC) 13
HRQOL scores were assessed with European Organization for Research and Treatment (EORTC), its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Subscales were scored on a range of 0 to 100. Higher symptom score = greater degree of symptom severity.
Time frame: Up to 33.8 months
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Sanatorio Duarte Quiros
Córdoba, Argentina
Centro Oncologico Riojano Integral
La Rioja, Argentina
Klinikum Klagenfurt Am Worthersee
Klagenfurt, Carinthia, Austria
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Halifax, Nova Scotia, Canada
Toronto University Health Network
Toronto, Ontario, Canada
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