Phase I Trial of 5-Azacitidine Plus Gemcitabine in Patients With Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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The primary objective is to determine the maximum tolerated dose (MTD) of azacitidine and gemcitabine in subjects with previously untreated and unresectable pancreatic cancer. Also to determine the effect of azacitidine therapy on DNA methylation in peripheral blood cells.

Detailed Description
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This is a Phase I single arm study designed for subjects with newly diagnosed, unresectable pancreatic cancer who have received no prior chemotherapy, radiation therapy, or surgery with curative intent for pancreatic cancer.

Official Title
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Phase I Trial of 5-Azacitidine Plus Gemcitabine in Patients With Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Vidaza


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have pathologically confirmed diagnosis of pancreatic adenocarcinoma Must have measurable disease as defined by RECIST. RECIST evaluation must have occurred within 4 weeks prior to study entry Must have newly diagnosed, unresectable disease and have received no prior chemotherapy, radiation therapy or surgery with curative intent for pancreatic cancer Karnofsky performance status of greater than or equal to 70% Other significant medical conditions must be well controlled and stable in the opinion of the investigator for at least 30 days prior to Study Day 1 Women of child bearing age must have negative serum pregnancy test prior to treatment Exclusion Criteria: Known central nervous system tumor involvement Evidence of other active malignancy requiring treatment Clinically significant heart disease Active serious systemic disease, including active bacterial or fungal infection Active viral hepatitis or symptomatic HIV infection. Positive serology alone is not exclusionary Prior surgery with curative intent for pancreatic cancer Prior or current chemotherapy or radiation therapy for pancreatic cancer. Palliative radiation for distant metastases (excluding metastases in the abdominal region) is allowed Breast feeding, pregnant, or likely to become pregnant during the study known or suspected hypersensitivity to azacitidine or mannitol

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: azacitabine<br> | Drug: Vidaza<br>* Vidaza will be administered subq daily for 5 consecutive days each 28-day cycle<br>* Other names: Azacitibine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine maximum tolerated dose | There will be 5 planned cohorts that will receive the escalating doses of azicitidine and gemcitabine. There will be at least 3 patients in each cohort | 28 days | 
| Toxicity | To describe the toxicity associated with the use of this combination regimen | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the effect of azacitidine therapy on DNA methylation in peripheral blood cells | Perform multivariable regression models to explore and assess associations among changes in DNA methylation in peripheral blood cells, chemo effect on tumor (stable disease or shrinkage based on scans) and changes in tumor markers. |  |