Clinical Trial: Ziv-Aflibercept in Treating and Computed Tomography Perfusion Imaging in Predicting Response in Patients With Pancreatic Neuroendocrine Tumors That Are Metastatic or Cannot Be Removed by Surgery

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Perfusion CT as Predictive Biomarker in a Phase II Study of Ziv-Aflibercept in Patients With Advanced Pancreatic Neuroendocrine Tumors

Brief Summary: This phase II trial studies ziv-aflibercept in treating and perfusion computed tomography perfusion imaging in predicting response in patients with pancreatic neuroendocrine tumors that have spread to other parts of the body or cannot be removed by surgery. Ziv-aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor. Diagnostic procedures, such as computed tomography perfusion, imaging may help measure a patient's response to ziv-aflibercept treatment.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Estimate the objective response rate (RR) of ziv-aflibercept among patients with advanced pancreatic neuroendocrine tumors (NET)s according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. Test the following hypotheses: that baseline perfusion computed tomography (CT) parameters can predict which patients with advanced pancreatic neuroendocrine tumors (pNETs) will respond to treatment with ziv-aflibercept.

SECONDARY OBJECTIVES:

I. Estimate progression free survival (PFS) duration among patients treated with ziv-aflibercept.

II. Evaluate the relationship between response rate and baseline blood volume (BV) and between response rate and baseline permeability surface (PS).

TERTIARY OBJECTIVES:

I. Determine whether post-treatment changes in BV expressed as relative change from baseline correlate with response to ziv-aflibercept.

II. Determine whether post-treatment tumor blood flow (BF) (absolute measurement) correlates with response to ziv-aflibercept.

III. Determine whether post-treatment changes in BF and, BV, expressed as relative change from baseline, correlate with relative change in sum of tumor diameters (RECIST 1.1 measurements).

IV. Determine the effect of ziv-aflibercept therapy on post-treatment BF, BV, mean transit time (MTT), and PS at 4 weeks after treatment.

V. Evaluate the changes in tumor perfusion parameters at time of progress
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective response rate according to RECIST 1.1 [ Time Frame: Up to 1 year ]

90% exact confidence interval will be constructed for the overall group and for all the marker subgroups respectively. Fisher's exact test will be applied to test the equal response rates between the two groups with a one-sided 5% type I error rate.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Baseline BV [ Time Frame: Baseline ]
    The relationship between response rate and baseline BV will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline BV separating responders and non-responders will be performed. Receiver operating characteristic (ROC) curves will be generated. Response rates of perfusion CT (pCT) subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).
  • Baseline PS [ Time Frame: Baseline ]
    The relationship between response rate and baseline PS will be evaluated. In addition to hypothesis testing using externally generated cut-points, refinement of optimal cut points in baseline PS separating responders and non-responders will be performed. ROC curves will be generated. Response rates of pCT subgroups defined by these cut-points will be compared using chi-square test. Response profiles of pCT subgroups defined by these cut-points will be compared using non-parametric test (Wilcoxon rank sum test).
  • PFS [ Time Frame: Up to 1 year ]
    Calculated for all eligible patients using the Kaplan Meier method and reported with confidence interval.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: March 28, 2014
Date Started: June 2014
Date Completion:
Last Updated: May 11, 2017
Last Verified: May 2017