A Phase II Study to Assess the Efficacy and Safety of Preoperative Chemo With Radiation Therapy for Patients With Borderline Unresectable Adenocarcinoma of the Pancreas

The purpose of this phase II clinical trial study is to assess the resection rate among
subjects who have been initially diagnosed with unresectable or borderline resectable
pancreatic adenocarcinoma. This will be done by providing preoperative treatment that will
include alternating cycles of chemotherapy and radiotherapy treatment. In addition, this
clinical trial will assess the safety of preoperative chemotherapy with radiation therapy for
subjects with unresectable or borderline resectable adenocarcinoma of the pancreatic head,
assess margin-negative resection rates, disease-free survival, assess overall survival rates,
and determine patterns of local and distant recurrence.

The study population in this clinical trial will consist of untreated subjects 18 years or
older who have a histologically or cytologically confirmed diagnosis of unresectable or
borderline resectable adenocarcinoma of the pancreatic head. Once the patient has undergone
the necessary tests and the tumor has been staged, the principal investigator or
co-investigators will determine if the patient is suitable to be inducted in this clinical
trial. The course of preoperative treatment in this study will consist of an alternating
combination of 6mg/M² of Gemzar for 24 hours and 7.0 Gy of radiation therapy. The subject
will undergo one of these therapies alternating daily for a total of 10 days then the subject
will be allowed to rest for 4 weeks before undergoing restaging and surgery. After surgery,
the subject will then undergo the conventional chemotherapy regimen consisting of 6 cycles of
1000mg/M² of Gemzar over a 30 minute infusion rate.

The primary outcome of this clinical trial is the margin-negative resection rate. This will
be determined by the tumor's response to the pre/post-operative treatment so that the tumor
can be removed surgically via pancreaticoduodenectomy. Once the subject has completed the
treatment as described in the protocol, he/she will continued to be followed to assess
survival and patterns of local and distance recurrence. The purpose of this clinical trial
will be an attempt to provide subjects with a more hopeful alternative to treatment for a
disease that otherwise offers a grim prognosis.

Inclusion Criteria:

1. Ages 18 years and above. There will be no upper age restriction.

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. (See Appendix A
-ECOG Performance Status Scale).

3. Cytologic or histologic proof of adenocarcinoma of pancreas.

4. Adequate renal, and bone marrow function:

1. Leukocytes >= 3,000/uL (upper limit)

2. Absolute neutrophil count >= 1,500/uL (upper limit)

3. Platelets >= 100,000/Ul

4. Serum creatinine <= 2.0 mg/dL

5. Hepatic function (endoscopic or percutaneous drainage as needed)

a. Aspartate aminotransferase (AST)-(SGOT)/Alanine aminotransferase (ALT) (SGPT) <= 5
X institutional ULN (upper limit of normal)

6. Borderline resectable pancreatic cancer:

1. Short segment hepatic artery abutment (< 180° involvement)

2. Tumor abutment (<180° ) of superior mesenteric artery

3. Superior mesenteric/portal vein involvement beyond that of a simple resection and
reconstruction

4. Pancreatitis that obscures the determination of vessel involvement and may
preclude an otherwise curative operation

7. Unresectable pancreatic cancer:

1. Tumors that encase (> 180° involvement) single or multiple arteries and veins
(celiac axis, superior mesenteric artery, superior mesenteric/portal vein,
hepatic artery)

2. Occlusion of superior mesenteric/portal vein

Exclusion Criteria:

1. Infections such as cholangitis, pneumonia, or wound infections that would preclude
protocol therapy.

2. Women with a positive urine or serum pregnancy test are excluded from this study;
women of childbearing potential (defined as those who have not undergone a
hysterectomy or who have not been postmenopausal for at least 24 consecutive months)
must agree to refrain from breast feeding and practice adequate contraception as
specified in the informed consent. Adequate contraception consists of oral
contraceptive, implantable contraceptives, injectable contraceptives, a double barrier
method, or abstinence.

3. Subjects cannot have known heptic or peritoneal metastases detected by ultrasound
(US), CT scan, or laparotomy/laparoscopy prior to treatment.

4. Subjects with unstable angina or New York Heart Association (NYHA) Grade II or greater
congestive heart failure will be excluded (see Appendix B).

5. Known presence of central nervous system or brain metastases

6. Subjects with prior radiotherapy to the upper abdomen or liver will be excluded.

7. Subjects will be excluded if deemed unable to comply with study and/or follow-up
procedures.

8. Subjects with a known hypersensitivity to Gemzar are excluded.

9. Multiple positive lymph nodes, which will make the radiotherapy treatment volume too
large. Peripancreatic involved nodes can be included in the radiotherapy treatment
volume if the field of involved nodes is less than 7.5cm.