Clinical Trial: Temozolomide With or Without Capecitabine in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors

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

Official Title: A Randomized Phase II Study of Temozolomide or Temozolomide and Capecitabine in Patients With Advanced Pancreatic Neuroendocrine Tumors

Brief Summary: This randomized phase II trial studies how well giving temozolomide with or without capecitabine works in treating patients with advanced pancreatic neuroendocrine tumors. Drugs used in chemotherapy, such as temozolomide and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether temozolomide is more effective with or without capecitabine in treating patients with advanced pancreatic neuroendocrine tumors.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

SECONDARY OBJECTIVES:

I. To evaluate response rates (RR) associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

II. To evaluate overall survival (OS) associated with temozolomide alone or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors.

III. To evaluate the toxicity associated with temozolomide alone or temozolomide and capecitabine treatment in patients with advanced pancreatic neuroendocrine tumors.

IV. To evaluate the usefulness of methyl guanine methyltransferase (MGMT) status (by immunohistochemistry [IHC] and promoter methylation) for predicting response in pancreatic neuroendocrine tumor patients treated with either temozolomide or temozolomide and capecitabine.

V. To bank radiology images for evaluation of quality, reproducibility, and compliance with computed tomography (CT) methodology.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive temozolomide orally (PO) once daily (QD) on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive capecitabine PO twice daily (BID) on days 1-14 an
Sponsor: Eastern Cooperative Oncology Group

Current Primary Outcome: PFS [ Time Frame: Up to 5 years ]

Original Primary Outcome: PFS [ Time Frame: Up to 5 years ]

There will be two log-rank tests conducted, an interim analysis at 76% information and a final analysis at 100% information (105 PFS events), projected to occur at 3 years from the start of accrual. The overall type I error will be controlled using an O'Brien-Fleming boundary function. If the repeated two-sided 95% confidence interval on the hazard ratio does not contain the target alternative hazard ratio of 0.64, consideration will be given to declaring the study negative and reporting the results.


Current Secondary Outcome:

  • RR defined by revised RECIST criteria version 1.1 [ Time Frame: Up to 5 years ]
    Compared between arms using a two-group Fisher's exact test at an overall two-sided 20% significance level. In addition, within each arm, a 90% confidence interval on the true objective response rate will be no wider than 21 percentage points.
  • Overall survival [ Time Frame: Up to 5 years ]
  • Toxicity rates using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]


Original Secondary Outcome:

  • RR defined by revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 [ Time Frame: Up to 5 years ]
    Compared between arms using a two-group Fisher's exact test at an overall two-sided 20% significance level. In addition, within each arm, a 90% confidence interval on the true objective response rate will be no wider than 21 percentage points.
  • Overall survival [ Time Frame: Up to 5 years ]
  • Toxicity rates using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ]


Information By: Eastern Cooperative Oncology Group

Dates:
Date Received: April 2, 2013
Date Started: May 2013
Date Completion:
Last Updated: March 8, 2016
Last Verified: March 2016