Celecoxib, Irinotecan and Concurrent Radiotherapy in Preoperative Pancreatic Cancer

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

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.

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.

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