Dovitinib Lactate in Treating Patients With Pancreatic Neuroendocrine Tumors
|Gastrinoma Glucagonoma Insulinoma Pancreatic Polypeptide Tumor Recurrent Islet Cell Carcinoma Somatostatinoma||Drug: dovitinib lactate Other: pharmacological study 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 Dovitinib (TKI-258) in Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors With and Without Prior VEGF-Inhibitor Therapy|
- Progression-free survival [ Time Frame: 6 months ]Confidence intervals for the estimate of 6-month PFS will be calculated using the method of Duffy and Santner.
- Time to treatment failure [ Time Frame: Calculated as the time between registration and the date of ending treatment, assessed up to 3 years ]Kaplan-Meier methodology will be used to estimate the distribution of survival and provide point estimates at various time points.
- Time to progression [ Time Frame: Calculated as the time between registration and disease progression, assessed up to 3 years ]Kaplan-Meier methodology will be used to estimate the distribution of survival and provide point estimates at various time points.
- Overall survival [ Time Frame: Estimated as the time between registration and death, assessed up to 3 years ]Kaplan-Meier methodology will be used to estimate the distribution of survival and provide point estimates at various time points.
- Duration of response [ Time Frame: Time from best response to the date of progressive disease (or date of last disease assessment, for patients having not progressed), assessed up to 3 years ]
- Biochemical response, classified according to RECIST v1.1 [ Time Frame: Up to 3 years ]Assessed using categorical data analysis.
- Radiographic response, classified according to RECIST v1.1 [ Time Frame: Up to 3 years ]Assessed using categorical data analysis.
- Incidence of adverse events graded according to National Cancer Institute (NCI) CTCAE version 4.0 [ Time Frame: Up to 3 years ]Maximum severity of each adverse event (AE) will be summarized using summary statistics, graphical techniques, and categorical methods, thereafter summarized by patient cohort. AEs will be also reviewed and summarized in consideration of relationship to study treatment (i.e., attribution).
- Change in circulating growth factors and soluble receptors (e.g., bFGF, VEGF, PLGF, sVEGFR1 and 2, collagen IV, FGF23) [ Time Frame: Baseline to 30 days after completion of study treatment ]The relationship between these biomarkers and clinical outcome in this patient population will be explored. Statistical methods include: two-sample t-tests with adjustment for multiple comparisons of continuous biomarker variables between treatment groups, Wilcoxon and Kruskal-Wallis tests and chi-square tests for ordinal categorical variables between groups, regression methods to assess the prognostic factors on molecular targets, and Kaplan-Meier survival methods for time to disease progression or time to target resistance.
- Banking of archival tissue for future research [ Time Frame: Baseline ]
- Plasma levels of circulating angiogenic factors and soluble receptors [ Time Frame: Up to 30 days after completion of study treatment ]The relationship between these biomarkers and clinical outcome will be explored in this patient population.
|Study Start Date:||October 2014|
|Study Completion Date:||May 2015|
|Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (dovitinib lactate)
Patients receive dovitinib lactate PO on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: dovitinib lactate
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
I. To evaluate the efficacy of dovitinib (dovitinib lactate) in patients with progressive well-differentiated neuroendocrine tumors of the pancreas (PNETs) in reference to 6-month progression free survival (PFS) historical-controlled patients and in two cohorts defined by prior vascular endothelial growth factor (VEGF)-inhibitor therapy (Cohort 1 - no prior VEGF, Cohort 2 - prior VEGF).
I. To determine the safety of dovitinib in patients with progressive well-differentiated PNETs.
II. To evaluate time to treatment failure, time to progression, and overall survival.
III. To evaluate radiographic and biochemical response rates.
I. To assess the pharmacodynamic effect of dovitinib on plasma biomarkers by measuring concentrations of circulating growth factors and soluble receptors (e.g. basic fibroblast growth factor [bFGF], VEGF, placental growth factor [PLGF], soluble VEGF receptor 1 (sVEGFR1) and 2, collagen IV, fibroblast growth factor 23 [FGF23]).
II. Archival tissue collected from patients prior to registration will be banked to later analyze baseline expression of potential biomarkers (e.g., bFGF, FGFR).
Patients receive dovitinib lactate orally (PO) on days 1-5, 8-12, 15-19, and 22-26. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months for 6 months, every 3 months for 6 months, and then periodically for 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02108782
|Principal Investigator:||Emily Bergsland||Academic and Community Cancer Research United|