Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.
|Malignant Neoplasm||Drug: ponatinib hydrochloride Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)|
- Overall response, defined as the number of patients who achieve any response according to disease type in the first 6 courses of treatment [ Time Frame: Up to 6 months ]The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.
- Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after last dose of study drug ]Frequency and severity of adverse events 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 for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.
- Tolerability of the regimen, assessed by the number of patients who required dose modifications and/or dose delays [ Time Frame: Up to 30 days after last dose of study drug ]Collected and summarized by descriptive statistics. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.
- Overall survival [ Time Frame: The time from treatment initiation to death, assessed up to 52 weeks ]Kaplan-Meier curves will be used to estimate the survival distribution.
- Progression free survival [ Time Frame: The time from treatment initiation to progression or death, assessed up to 52 weeks ]Kaplan-Meier curves will be used to estimate the survival distribution.
- Clinical benefit rate (CBR) [ Time Frame: 6 months ]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 CBR will be calculated.
- Correlative gene and protein markers [ Time Frame: Up to 3 years (time of progression) ]Correlative gene 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 vs. no response). Overall, hypothesis testing will largely be avoided given the sample size limitations.
|Actual Study Start Date:||February 24, 2015|
|Estimated Study Completion Date:||December 31, 2017|
|Estimated Primary Completion Date:||December 31, 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (ponatinib hydrochloride)
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: ponatinib hydrochloride
Other Names:Other: laboratory biomarker analysis
I. To evaluate the response of ponatinib (ponatinib hydrochloride) in patients with fibroblast growth factor receptor (FGFR) altered cancers.
I. To assess the safety and tolerability of ponatinib in advanced solid tumors with genomic FGFR alterations.
II. To assess progression free survival (PFS) and overall survival (OS) with ponatinib.
III. To determine candidate genomic and proteomic biomarkers of sensitivity and resistance to ponatinib using unbiased high throughput approaches (exome, transcriptome, reverse phase protein array [RPPA]).
IV. To assess response of ponatinib in advanced cancers with subsets of genomic FGFR alterations (fusions vs. amplifications vs. mutations).
Patients receive ponatinib hydrochloride 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 for 52 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02272998
|Contact: The Ohio State University Comprehensive Cancer Center||1-800-293-5066||Jamesline@osumc.edu|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Ajjai Alva, MD 734-936-8906 Ajjai@med.umich.edu|
|Principal Investigator: Ajjai Alva|
|United States, Ohio|
|Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Sameek Roychowdhury, MD 614-685-5842 Sameek.Roychowdhury@osumc.edu|
|Principal Investigator: Sameek Roychowdhury, MD|
|Principal Investigator:||Sameek Roychowdhury, MD, PhD||Ohio State University Comprehensive Cancer Center|