Clinical Trial: Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase I/II Study of the Combination of Temozolomide and Pazopanib in Advanced Pancreatic Neuroendocrine Tumors (PNET)

Brief Summary: This phase I/II trial studies the side effects and best dose of temozolomide and pazopanib hydrochloride when given together and to see how well they work in treating patients with advanced pancreatic neuroendocrine tumors (PNET) that cannot be removed by surgery. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for tumor growth. Giving temozolomide together with pazopanib hydrochloride may be an effective treatment for patients with PNET.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of temozolomide and pazopanib (pazopanib hydrochloride) combination in patients with advanced PNET. (Phase I) II. Determine the overall response rate (ORR). (Phase II)

SECONDARY OBJECTIVES:

I. Determine safety and toxicity profile of the combination of temozolomide and pazopanib in this population. (Phase I) II. Describe the pharmacokinetics of temozolomide alone and in combination with pazopanib. (Phase I) III. Observe the ORR. (Phase I) IV. Determine progression-free survival (PFS) and overall survival (OS), disease control rate (DCR), and duration of response (DOR). (Phase II) V. Determine the safety and toxicity profile of the combination in a larger cohort of patients. (Phase II)

TERTIARY OBJECTIVES:

I. Examine the relationship between tumor blood flow, as measured by perfusion functional computed tomography (f CT), and overall response.

II. Correlate the expression of tissue methyl-guanine methyl transferase (MGMT) as measured by immunohistochemistry (IHC) with ORR and PFS.

OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.

Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 and 15-21 and pazopanib hydrochloride PO 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 every 3 months.

Current Primary Outcome:

• Number of dose limiting toxicities in patients treated with this regimen [ Time Frame: After 28 days (1 course of treatment) ]
  For patients in the Phase I portion: Toxicity will be assessed according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The number of patients experiencing dose limiting toxicities at a particular level will determine whether the dose can be tolerated.
• Number of patients responding to treatment [ Time Frame: After two courses of treatment (8 weeks) ]
  For patients in the Phase II portion: Patients will have a CT scan after two courses of treatment to determine whether their disease is responding to treatment.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Number of toxicity events noted in patients undergoing this treatment. [ Time Frame: Weekly during the first course of treatment (Every 28 days) and then Bi-Weekly thereafter as long as patients are on treatment ]
  For Patients in Phase I: Symptoms and Lab Results will be reviewed with patients according to this schedule.
• Amount of pazopanib in the blood at various timepoints after administration [ Time Frame: Multiple timepoints during Days 1-3 of course 1 (see description) ]
  For the Six Patients in Phase I portion who are enrolled in the PK cohort: Blood will be drawn on Day 1 before beginning treatment and again at 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after beginning treatment. On Day 2- 24 hours after the first dose from Day 1, and again 10 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours after taking the second dose. Day 3 - 24 hours after the second dose from Day 2.
• Number of years that patients survive without experiencing disease progression [ Time Frame: Baseline and after every 2 courses of treatment (8 weeks) ]
  For Patients in Phase II Portion: The Length of time between when the patient begins treatment and when disease progression is first noted will be calculated.
• Number of years that patients survive after undergoing study treatment [ Time Frame: Baseline and after every 2 courses of treatment (8 weeks) ]
  For Patients in Phase II Portion: The Length of time between when the patient begins treatment and when and when the patient becomes deceased will be calculated.
• Number of patients experiencing response to treatment or stable disease [ Time Frame: After every 2 courses of treatment (8 weeks) ]
  For Patients in Phase II Portion: The number of patients demonstrating the complete response, partial response or stable disease after 8 weeks of treatment will be calculated.
• Number of months that patients maintain a response to treatment until disease progression or death [ Time Frame: After every 2 courses of treatment (8 weeks) ]
  For Patients in Phase II Portion: The time patients start receiving treatment until disease progression will be calculated.
• Determine the Relationship between tumor blood flow and Overall Response Rate [ Time Frame: At Baseline and after two corurses of treatment (8 weeks) ]
  For Patients in Phase II Portion: Patients will have a perfusion functional computed tomography (fCT) scan at baseline and after two courses of treatment.
• Amount of a particular tumor biomarker in blood as correlated with progression free survival [ Time Frame: Baseline and at Response assessment after two courses of treatment (8 weeks) ]
  For Patients in Phase II Portion: The level of expression of tissue methyl-guanine methytransferase (MGMT)will be measured in tissue from the diagnostic biopsy and these results will be correlated with response rate.

Original Secondary Outcome: Same as current

Information By: Northwestern University

Dates:
Date Received: October 4, 2011
Date Started: November 2011
Date Completion: August 2018
Last Updated: October 10, 2016
Last Verified: October 2016