Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery
Pancreatic Alpha Cell Carcinoma
Pancreatic Beta Islet Cell Carcinoma
Pancreatic Delta Cell Carcinoma
Pancreatic G-cell Carcinoma
Recurrent Islet Cell Carcinoma
Drug: pazopanib hydrochloride
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of the Combination of Temozolomide and Pazopanib in Advanced Pancreatic Neuroendocrine Tumors (PNET)|
- Number of dose limiting toxicities in patients treated with this regimen [ Time Frame: After 28 days (1 course of treatment) ] [ Designated as safety issue: Yes ]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) ] [ Designated as safety issue: No ]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.
- 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 ] [ Designated as safety issue: Yes ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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) ] [ Designated as safety issue: No ]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.
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (chemotherapy and enzyme inhibitor)
Patients receive temozolomide PO 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.
Other Names:Drug: pazopanib hydrochloride
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)
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)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01465659
|Contact: Study Coordinatorfirstname.lastname@example.org|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Halla null. Nimeiri 312-695-4381 email@example.com|
|Principal Investigator: Halla null. Nimeiri|
|United States, Michigan|
|University of Michigan||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Mark M. Zalupski 734-615-3969 firstname.lastname@example.org|
|Principal Investigator: Mark M. Zalupski|
|United States, Pennsylvania|
|Fox Chase Cancer Center||Recruiting|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|Contact: Steven J. Cohen 215-728-2570 Steven.Cohen@fccc.edu|
|Principal Investigator: Steven J. Cohen|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Contact: Jordan D. Berlin 615-936-8422 jordan.berlin@Vanderbilt.edu|
|Principal Investigator: Jordan D. Berlin|
|United States, Washington|
|University of Washington Seattle Cancer Care Alliance||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Gabriela Chiorean, MD 855-557-0555|
|Principal Investigator:||Halla Nimeiri||Northwestern University|