A Phase I Study of Induction AMG 479 and Gemcitabine, Followed by AMG 479, Capecitabine, and 3D-Conformal Radiation Therapy (3D-CRT) With Subsequent Maintenance Therapy for Locally Advanced Pancreatic Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Pathologically confirmed (histologic or cytologic) locally advanced adenocarcinoma of
the pancreas

- Patients must have unresectable disease based on institutional standardized
criteria of unresectability or medical inoperability

- Patients with or without regional adenopathy are eligible

- No distant metastases based upon the following minimum diagnostic workup:

- History and/or physical examination, including collection of weight and vital
signs, within 28 days prior to study entry

- Abdominal and/or pelvic CT scan with IV contrast or MRI scan within 21 days
prior to study entry

- Chest CT scan or whole-body PET/CT within 21 days prior to study entry

- No second malignancy or peritoneal seeding

PATIENT CHARACTERISTICS:

- Zubrod performance status 0-1

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin (Hgb) ≥ 10.0 g/dL (the use of transfusion or other intervention to achieve
Hgb ≥ 10.0 g/dL is acceptable)

- Glycosylated hemoglobin (HgbA1c) ≤ 8%

- Serum creatinine ≤ 1.5 mg/dL

- ALT or AST < 3 times upper limit of normal (ULN)

- Total bilirubin < 3.0 mg/dL

- Alkaline phosphatase < 3 times ULN

- Fasting blood glucose < 160 mg/dL

- Patients with a non-fasting blood glucose > 160 mg/dL (8.9 mmol/L) must have a
fasting blood glucose ≤ 160 mg/dL (8.9 mmol/L) in order to be eligible

- No grade 2 or worse hearing impairment

- Negative serum pregnancy test (if applicable)

- Women of childbearing potential and men who are sexually active must be willing/able
to use medically acceptable forms of contraception during the course of the study,
and for 3 months (6 months for men) after the last study drug administration

- Not pregnant or nursing

- Ability to swallow oral medications

- At least 3 years since prior malignancy except non-melanomatous skin cancer or
carcinoma in situ of the breast, oral cavity, or cervix

- No severe active co-morbidity, defined as any of the following:

- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 6 months

- Transmural myocardial infarction within 6 months prior to study entry

- Acute bacterial or fungal infection requiring intravenous antibiotics at the
time of registration

- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization, or precluding study therapy within 30 days before
registration

- Uncontrolled malabsorption syndrome significantly affecting gastrointestinal
function

- Any unresolved bowel or bile duct obstruction

- Major resection of the stomach or small bowel that could affect the absorption
of capecitabine

- Acquired immune deficiency syndrome (AIDS) based upon current Centers for
Disease Control and Prevention (CDC) definition

- HIV testing is not required for entry into this protocol

- Existing venous thromboembolism requiring anti-coagulation therapy

- No prior allergic reaction to capecitabine or gemcitabine hydrochloride

PRIOR CONCURRENT THERAPY:

- No prior systemic chemotherapy for pancreatic cancer

- Prior chemotherapy for malignancies other than pancreatic cancer is allowed
provided chemotherapy was completed > 3 years prior to study entry

- No prior radiotherapy to the region of the study cancer that would result in overlap
of radiation therapy fields

- More than 28 days since any prior major surgery

- Insertion of a vascular access device, insertion of a biliary stent, exploratory
laparotomy, or laparoscopy are not considered major surgery

- No prior ganitumab

- Patients requiring concurrent oral anticoagulants (e.g., Coumadin, warfarin) are
eligible provided there is increased vigilance with respect to monitoring INR

- No concurrent participation in another clinical treatment trial

- No concurrent intensity-modulated radiotherapy

- No other concurrent therapy including the following:

- Other investigational or approved chemotherapeutic agents

- Other monoclonal antibody

- Sorivudine or brivudine A

- Cimetidine

- G-CSF agents