Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers
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|ClinicalTrials.gov Identifier: NCT03868423|
Recruitment Status : Recruiting
First Posted : March 11, 2019
Last Update Posted : January 18, 2020
|Condition or disease||Intervention/treatment||Phase|
|Advanced Malignant Neoplasm ALK Fusion Protein Expression ALK Gene Amplification ALK Gene Mutation Locally Advanced Malignant Solid Neoplasm Metastatic Malignant Neoplasm in the Brain Metastatic Malignant Neoplasm in the Central Nervous System Metastatic Malignant Solid Neoplasm ROS1 Fusion Positive ROS1 Gene Amplification ROS1 Gene Mutation||Drug: Brigatinib Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Other: Questionnaire Administration||Phase 2|
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).
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]).
I. Correlation of brigatinib exposure with efficacy and safety. II. Correlation of tumor and plasma biomarkers with brigatinib efficacy and safety.
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 (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of Brigatinib for Advanced Solid Cancers Harboring Genomic Alterations in ALK (Excluding Lung) and ROS1 Oncogenes|
|Actual Study Start Date :||March 20, 2019|
|Estimated Primary Completion Date :||December 30, 2020|
|Estimated Study Completion Date :||December 30, 2020|
Experimental: Treatment (brigatinib)
Patients receive brigatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
- Overall response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: Up to 52 weeks ]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.
- Confirmed objective response rate (ORR) [ Time Frame: Up to 52 weeks ]Will be assessed by central independent review committee per RECIST version 1.1.
- Time to response [ Time Frame: Up to 52 weeks ]Will be evaluated.
- Duration of response [ 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 ]Will be evaluated.
- Time on treatment [ Time Frame: Up to 52 weeks ]Will be evaluated.
- Disease control rate [ Time Frame: Up to 52 weeks ]Will be assessed by RECIST version 1.1.
- Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 52 weeks ]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.
- Overall survival [ Time Frame: From treatment initiation to death due to any cause, assessed up to 52 weeks ]Kaplan-Meier curves will be used to estimate the survival distributions of overall survival.
- 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 ]Kaplan-Meier curves will be used to estimate the survival distributions of progression-free survival.
- Clinical benefit rate [ Time Frame: 6 months ]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.
- Rate of participation of those screened and identified with the eligible genetic alterations [ Time Frame: Up to 52 weeks ]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.
- Rate of enrollment of those screened and identified with the eligible genetic alterations [ Time Frame: Up to 52 weeks ]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.
- Brigatinib exposure [ Time Frame: Up to 52 weeks ]Brigatinib exposure will be compared to RECIST measurements and adverse events measured using CTCAE v4.
- Correlative gene and protein markers [ Time Frame: Up to 52 weeks ]Correlative and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response versus no response). Will correlate with efficacy and safety.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03868423
|Contact: The Ohio State University Comprehensive Cancer Center||800-293-5066||OSUCCCClinicaltrials@osumc.edu|
|Contact: Shona Taylorfirstname.lastname@example.org|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Sameek Roychowdhury, MD 614-685-5841 email@example.com|
|Principal Investigator: Sameek Roychowdhury, MD|
|Principal Investigator:||Sameek Roychowdhury, MD||Ohio State University Comprehensive Cancer Center|