Temozolomide and Pazopanib Hydrochloride in Treating Patients With Advanced Pancreatic Neuroendocrine Tumors That Cannot Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT01465659|
Recruitment Status : Active, not recruiting
First Posted : November 6, 2011
Results First Posted : June 17, 2020
Last Update Posted : June 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Alpha Cell Carcinoma Pancreatic Beta Islet Cell Carcinoma Pancreatic Delta Cell Carcinoma Pancreatic G-cell Carcinoma Recurrent Islet Cell Carcinoma||Drug: temozolomide Drug: pazopanib hydrochloride||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study of the Combination of Temozolomide and Pazopanib in Advanced Pancreatic Neuroendocrine Tumors (PNET)|
|Actual Study Start Date :||December 12, 2011|
|Actual Primary Completion Date :||July 30, 2018|
|Estimated Study Completion Date :||August 2021|
Experimental: Temozolomide 100 mg/m2 and Pazopanib 400 mg
Temozolomide 100 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28
Drug: pazopanib hydrochloride
Experimental: Temozolomide 75 mg/m2 and Pazopanib 400 mg
Temozolomide 75 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28
Drug: pazopanib hydrochloride
Experimental: Temozolomide 150 mg/m2 and Pazopanib 400 mg
Temozolomide 150 mg/m2 on days 1-7 and 15-21 , Pazopanib 400 mg on days 1-28
Drug: pazopanib hydrochloride
- Determine the Maximum Tolerated Dose (MTD) of Temozolomide and Pazopanib Combination in Patients With Advanced Pancreatic Neuroendocrine Tumor (PNET) in Phase I [ Time Frame: After 28 days (1 course of treatment) ]MTD and recommended phase II dose (RP2D) determination for the combination of temozolomide and pazopanib in patients with advanced PNET will be achieved using a standard "3+3" dose escalation/de-escalation design. After each 3 patients are enrolled into the study, further enrollment will be temporarily suspended until safety has been reviewed for the first 28 days of treatment to determine if dose limiting toxicities have been experienced by patients and if a further 3 patients should be enrolled at the current dose or dose escalation/de-escalation for the next 3 patients should occur.
- Overall Response Rate (ORR) in Patients With Advanced Neuroendocrine Tumors (PNET) Treated With Temozolomide and Pazopanib Combination Treatment at the RP2D in Phase II [ Time Frame: After two courses of treatment (8 weeks) ]
Overall response rate will be determined by the number of patients who's best response as assessed by RECIST 1.1 is complete response (CR) and partial response (PR) in patients with PNET that are enrolled at the recommended phase II dose (RP2D) (PK cohort included).
CR= Disappearance of all target lesions PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01465659
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|United States, Washington|
|University of Washington Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Halla Nimeiri||Northwestern University|