Ultrasound-Guided Photodynamic Therapy With Photofrin & Gemcitabine for Patients With Locally Advanced 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