A Phase II Study of Pioglitazone for Patients With Cancer of the Pancreas

Study Overview
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Brief Summary
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This study is being done to determine whether or not addition of the oral medication, pioglitazone to standard chemotherapy, results in improvement of blood tests that measure the body's ability to utilize sugar (glucose and insulin metabolism). In addition the investigators want to determine whether or not treatment with pioglitazone results in (1) improvement in the size of the tumor, (2) weight gain, (3) improved ability to function during the day and (4) quality of life.

Official Title
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A Phase II Study of Pioglitazone for Patients With Cancer of the Pancreas

Conditions
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Cancer of the Pancreas

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Histologically proven adenocarcinoma of the pancreas Radiologically measurable disease ECOG functional status 0-2 Exclusion Criteria: Prior radiation therapy for pancreatic cancer If chemotherapy is planned, new chemotherapy regimen should have started more than 14 days prior to enrollment Surgery or radiation planned within 8 weeks of starting therapy Prior exposure to Thiazolidinedione (TZD) therapy in the past 12 months Hypersensitivity of TZD New York heart association class III/IV heart failure. Known HIV positive Pregnant or lactating women History of, or active bladder cancer Inadequate hepatic function documented within 14 days of enrollment Total bilirubin level > 1.5 x ULN AST and ALT > 2.5 x ULN, unless there are liver metastases in which case AST and ALT or > 5 x ULN

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone & Chemotherapy in Patients without Diabetes<br> | Drug: Pioglitazone<br> <br> |
| Experimental: Pioglitazone & Chemotherapy in Patients with Diabetes<br> | Drug: Pioglitazone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Adiponectin Level | We will obtain serum levels of adiponectin at baseline and after 8 weeks of treatment with pioglitazone. | Baseline and 8 weeks of treatment with pioglitazone | 
| Change in Standard Glucose Tolerance Test | We will perform the area under the oral glucose tolerance test at baseline and after 8 weeks of treatment with pioglitazone. | Baseline to 120 minutes post glucose bolus | 
| Glucose to Insulin Ratio | Glucose to insulin ratio will be measured by taking the ratio of fasting level of serum glucose and insulin. We will obtain serum levels of fasting glucose and insulin every four weeks in all patients receiving pioglitazone | Every 4 weeks while receiving treatment, up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight | To describe changes in weight in patients with pancreas cancer receiving pioglitazone. | Baseline and every two weeks for 10 weeks, change between baseline and week 10 reported. | 
| Number of Patients With Objective Response | Objective response is the proportion of patients with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). | 8 weeks of treatment with pioglitazone | 
| Change in Patients' Performance Status by the Eastern Oncology Cooperative Group (ECOG) Scale of Performance Status | The ECOG Scale of Performance Status measures patients' performance status. Possible grades range from 0 to 5, with lower grade indicating a better performance status. | Baseline and 8 weeks of treatment with pioglitazone | 
| Change in Quality of Life by the FACT-Hep Scale | The FACT-Hep Scale (version 4) measures quality of life, It consists of five subscales: (1) physical well-being (PWB); (2) social and family well-being (SFWB); (3) emotional well-being (EWB); (4) functional well-being (FWB); and the hepatobiliary cancer subscale (HepCS). Possible scores range from 0 to 180, with lower scores indicating a better quality of life | Baseline and 8 weeks of treatment with pioglitazone | 
| Change in Pancreatic Intratumor Fat | Change in pancreatic intratumor fat will be measured by MRI | Baseline and 8 weeks of treatment with pioglitazone | 
| Change in Body Fast Distribution | Change in body fast distribution will be measured by MRI | Baseline and 8 weeks of treatment with pioglitazone | 
| Changes in Serum and MRI End Points | Compare changes in serum and MRI end points between pioglitazone | Baseline and 8 weeks of treatment with pioglitazone |