Celecoxib, Irinotecan and Concurrent Radiotherapy in Preoperative Pancreatic Cancer

Study Overview
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Brief Summary
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The purposes of this study are to examine the effects of a new combination of drugs, celecoxib (Celebrex®) and irinotecan (CPT-11), with standard radiation therapy on people before they undergo surgery; to determine what effects this combination has on pancreatic cancer; and to determine the highest dose of celecoxib and irinotecan that can be given safely without causing severe side effects. While not an endpoint, it is hoped that this combination will also shrink tumors enough for excision.

Detailed Description
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The purposes of this study are to examine the effects of a new combination of drugs, celecoxib (Celebrex®) and irinotecan (CPT-11), with standard radiation therapy on people before they undergo surgery; to determine what effects this combination has on pancreatic cancer; and to determine the highest dose of celecoxib and irinotecan that can be given safely without causing severe side effects. While not an endpoint, it is hoped that this combination will also shrink tumors enough for excision.

Official Title
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A Phase I Study of Celecoxib, Irinotecan and Concurrent Radiotherapy in the Preoperative Treatment of Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: celecoxib
* Drug: irinotecan
* Procedure: concurrent radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced carcinoma of the pancreas Arterial invasion or encasement Invasion/encasement of the portomesenteric veins Patients who have been previously denied operation Obstructive jaundice must be drained with a polyethylene biliary stent or surgical bypass prior to beginning treatment. White blood cell count > 3500 per ml and platelet count > 100,000 per ml Serum creatinine ≤ 1.5 mg/dl Bilirubin ≤ 1.5 ECOG performance status < 2 Exclusion Criteria: Prior chemotherapy, radiotherapy, or investigational agents for pancreatic cancer Evidence of distant metastasis or malignant lymphadenopathy Concurrent malignancies History of allergic reactions to celecoxib or to sulfa drugs No non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, magnesium or aluminum containing antacids, fluconazole or lithium may be administered within 5 days of study entry, during the study and for the 30 days following the completion of all study treatments. Pregnant women and lactating women Uncontrolled or serious intercurrent illness HIV-positive patients receiving combination antiretroviral therapy

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: 1<br>Celecoxib, Irinotecan and Concurrent Radiotherapy | Drug: celecoxib<br>* Patients will start celecoxib (200mg PO BID) beginning 3-5 days prior to chemoradiation at home and receive the drug until 30 days following the completion of chemoradiation.<br>* Other names: Celebrex;Drug: irinotecan<br>* Preoperative chemoradiation will consist of escalating doses of irinotecan (30 50 mg/m2 IV) once weekly for a total of 4 doses.<br>* Other names: Camptosar;Procedure: concurrent radiotherapy<br>* 50.4 cGy of standard external beam radiation. The radiation will be given in 28 treatments of 1.8 cGy per treatment over 5.5 weeks. This will be given in an outpatient setting.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine efficacy of combination of irinotecan, celecoxib and concurrent radiotherapy on pancreatic cancer; determine highest/safest doses of these drugs |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor diminishment for safe excision |  | 75 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced pancreatic cancer, invasion of major arteries and veins around pancreas, No prior radiation or chemo