This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the overall response rate (ORR) of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors). SECONDARY OBJECTIVES: I. To assess the safety and tolerability of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors). II. To assess progression free survival (PFS) and overall survival (OS) in patients with advanced ALK or ROS1 mutated solid tumors treated with brigatinib. III. To assess sensitivity and durability of response to brigatinib in different solid tumor types. IV. To assess the role of intertumoral and intratumoral heterogeneity in the development of resistance to brigatinib. V. To identify candidate genomic (including circulating tumor deoxyribonucleic acid \[DNA\]) and proteomic biomarkers of tumor sensitivity and resistance to brigatinib using high-throughput approaches (exome, transcriptome, reverse phase protein array \[RPPA\]). TERTIARY OBJECTIVES: I. Correlation of brigatinib exposure with efficacy and safety. II. Correlation of tumor and plasma biomarkers with brigatinib efficacy and safety. OUTLINE: Patients receive brigatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 52 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
90 mg orally QD for 7 days followed by 180 mg orally QD continuously thereafter. One cycle of therapy will consist of 28 days of treatment.
Correlative studies
Ancillary studies
Ancillary studies
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States
Overall response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Response for tumors will be assessed using the RECIST 1.1 criteria (using computed tomography scans or calipers by clinical exam) where response will be defined as a partial or complete response. Will be calculated with 95% binomial confidence intervals for the estimate of the proportion of responses.
Time frame: Up to 52 weeks
Confirmed objective response rate (ORR)
Will be assessed by central independent review committee per RECIST version 1.1.
Time frame: Up to 52 weeks
Time to response
Will be evaluated.
Time frame: Up to 52 weeks
Duration of response
Will be evaluated.
Time frame: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 52 weeks
Time on treatment
Will be evaluated.
Time frame: Up to 52 weeks
Disease control rate
Will be assessed by RECIST version 1.1.
Time frame: Up to 52 weeks
Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Time frame: Up to 52 weeks
Overall survival
Kaplan-Meier curves will be used to estimate the survival distributions of overall survival.
Time frame: From treatment initiation to death due to any cause, assessed up to 52 weeks
Progression-free survival
Kaplan-Meier curves will be used to estimate the survival distributions of progression-free survival.
Time frame: From the date of study registration to the date of event (ie, death and/or disease progression) or the date of last follow-up if no event has occurred, up to 52 weeks
Clinical benefit rate
Will be calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for clinical benefit rate will be calculated.
Time frame: 6 months
Rate of participation of those screened and identified with the eligible genetic alterations
The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset.
Time frame: Up to 52 weeks
Rate of enrollment of those screened and identified with the eligible genetic alterations
The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset. Genes will be evaluated in aggregate from whole exome and transcriptome sequencing.
Time frame: Up to 52 weeks
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