This phase I trial studies the side effects and best dose of ultrasound-guided photodynamic therapy with porfimer sodium when given together with gemcitabine hydrochloride in treating patients with locally advanced pancreatic cancer. Photodynamic therapy uses a drug, porfimer sodium, that becomes active when it is exposed to a certain kind of light. When the drug is active, cancer cells are killed. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving photodynamic therapy together with gemcitabine hydrochloride may be effect in patients with pancreatic cancer.

PRIMARY OBJECTIVES:

I. To determine the safety of increasing porfimer sodium (PHO) dose and total energy by endoscopic ultrasound (EUS)-guided photodynamic therapy (PDT) for locally advanced unresectable pancreatic cancer (PC) in humans.

SECONDARY OBJECTIVES:

I. Quantify computed tomography (CT) detected volume of tumor necrosis produced by EUS-PDT.

II. Quantify rates of tumor size stabilization or decrease by EUS PDT and determine objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. Determine surgical downstaging off of abdominal vessels and resectability. IV. Determine changes in serum cancer antigen (CA) 19-9 levels with treatment. V. Evaluate progression-free and overall survival.

OUTLINE: This is a dose-escalation study of EUS-PDT with porfimer sodium.

Patients receive porfimer sodium intravenously (IV) on day 1 and undergo EUS-PDT on days 1, 3, 8, and 21. After completion of EUS-PDT, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15 of courses 1 and 2 and on day 22 of courses 3 and 5. During courses 1-5, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After course 5, treatment with gemcitabine hydrochloride repeats every 2 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Unresectable, locally advanced measurable (at least bidirectional) adenocarcinoma of the pancreas (regardless of site) proven by biopsy or cytology and confirmed by surgical consultation
• Informed consent and authorization for the release of health information signed by the patient
• Karnofsky performance status >= 70%
• Life expectancy >= 3 months
• Females of childbearing potential and males must use an effective method of contraception

Exclusion Criteria:

• Metastatic (stage IV) disease (including involvement of the colon, adrenals, or kidney, or radiographic evidence of peritoneal seeding or pulmonary metastases)
• Previous chemotherapy, radiotherapy of other treatment for PC
• Gastric or duodenal wall invasion by the primary PC as assessed by CT or MRI and EUS staging
• Gastric or duodenal ulcer (at least 10 mm in size) within 10 mm of expected endoscopy puncture site(s) for PDT
• Esophageal or gastric varices
• Cystic component >= 25% the total volume of the tumor
• Ascites detected by CT, ultrasound (US) or MRI; (trace ascites will not be an exclusion)
• Bulky celiac adenopathy (i.e., >= 2.5 cm in diameter)
• Diagnosis of islet cell tumor, lymphoma, metastatic lesion, acinar cell (or other atypical pathologic malignancy)
• History of other malignancy in the past 2 years except carcinoma in situ of the cervix or bladder, non-melanomatous skin cancer or localized/early stage prostate cancer
• Unable to receive or previously intolerant of moderate and/or deep sedation
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x upper limit of normal (ULN)
• Total bilirubin >= 3 x ULN
• Alkaline phosphatase >= 3 x ULN
• International normalized ratio (INR) >= 1.5
• Partial thromboplastin time (PTT) ratio >= 1.5
• Serum creatinine >= 2.0 mg/dL
• Hematocrit =< 28% or hemoglobin =< 9 g/dL, but may have red blood cell (RBC) transfusion
• Platelet count =< 100,000/microliter (uL)
• Absolute neutrophil count (ANC) =< 1500/uL
• Clinically significant pancreatitis within 12 weeks of treatment with protocol therapy
• Contraindication to EUS-guided needle puncture into the pancreas
• History of coagulopathy or known thrombophilias
• Use of anticoagulants that cannot be discontinued both 5 days before and 5 days after EUS
• Clinical evidence of active infection of any type, including hepatitis B or C virus
• Pregnant or lactating women
• Experimental medications within the last 4 weeks prior to day 1
• Any surgery (including diagnostic laparoscopy and/or biliary +/- duodenal palliative bypass for inoperable PC) within the 2 weeks prior to day 1 of study protocol
• Chronic systemic corticosteroid use at superphysiologic doses (>= 10 mg prednisone per day or equivalent)
• Inability to avoid exposure of skin or eyes to direct sunlight or bright indoor light for at least 30 days
• Porphyria
• Inability to obtain venous access in the antecubital region to administer PHO or sedation for endoscopy procedures
• Significant concurrent medical or psychiatric illness which, in the opinion of the principal investigator would interfere with trial participation