Clinical Trial: Dovitinib Lactate in Treating Patients With Pancreatic Neuroendocrine Tumors

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: Phase II Study of Dovitinib (TKI-258) in Progressive, Well-Differentiated Pancreatic Neuroendocrine Tumors With and Without Prior VEGF-Inhibitor Therapy

Brief Summary: This phase II trial studies how well dovitinib lactate works in treating patients with pancreatic neuroendocrine tumors. Dovitinib lactate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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).

OUTLINE:

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 trea
Sponsor: Academic and Community Cancer Research United

Current Primary Outcome: 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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).


Original Secondary Outcome: Same as current

Information By: Academic and Community Cancer Research United

Dates:
Date Received: January 7, 2014
Date Started: October 2014
Date Completion:
Last Updated: July 29, 2015
Last Verified: July 2015