Panitumumab, Chemotherapy, and External-Beam Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot be Removed by Surgery

OBJECTIVES:

Primary

• To evaluate the 1-year survival rate in patients with locally advanced pancreatic cancer treated with panitumumab and continuous infusion fluorouracil administered concurrently with external-beam radiotherapy followed by gemcitabine and panitumumab.

Secondary

• To determine overall survival, time to disease progression, confirmed response rate, duration of response, and time to treatment failure in patients treated with this regimen.
• To determine adverse events in patients treated with this regimen.

OUTLINE:

• Panitumumab and chemoradiotherapy : Patients undergo external-beam radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-38. Patients also receive panitumumab IV over 1 hour on days 1, 15, and 29 and fluorouracil IV continuously over 24 hours daily OR oral capecitabine twice daily beginning on day 1 and continuing through the last day of radiotherapy.
• Panitumumab and chemotherapy: Beginning 4-6 weeks after completion of panitumumab and chemoradiotherapy, patients receive panitumumab IV over 1 hour on days 1 and 15 and gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for 3 courses. Patients then proceed to maintenance therapy.
• Maintenance therapy: Patients receive panitumumab IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed unresectable adenocarcinoma of the pancreas

• Including subtotal resection and gross residual disease

• No microscopic residual disease only
• Measurable disease is not required
• Disease is encompassable within standard radiotherapy fields for pancreatic cancer
• No evidence of metastatic disease outside of the planned radiotherapy field
• No cystadenocarcinoma of the pancreas or pancreatic tumors of neuroendocrine origin
• No distant metastases (i.e., liver or lung metastases or peritoneal spread)
• No history or known presence of CNS metastases

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/mm³
• Total bilirubin ≤ 3 times upper limit of normal (ULN)* NOTE: *Biliary stent placement or surgical bypass should be considered prior to treatment if impending bile duct obstruction by tumor
• AST ≤ 3 times ULN
• Creatinine ≤ 2.0 times ULN
• Magnesium normal
• Willing to return to an North Central Cancer Treatment Group (NCCTG) institution for follow-up
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for at least 6 months after treatment with panitumumab
• No prior or concurrent malignancy unless disease-free ≥ 3 years except for non-melanoma skin cancer, carcinoma in situ of the cervix, or organ confined prostate cancer with Gleason score < 7
• No nausea or vomiting > grade 1
• No uncontrolled intercurrent illness including, but not limited to, any the following:

• Ongoing or active infection
• Psychiatric illness or social situations that would limit compliance with study requirements
• No New York Heart Association clinically significant cardiovascular disease ≥ grade 2, including any of the following within the past year:

• Myocardial infarction
• Unstable angina
• Symptomatic congestive heart failure
• Serious, uncontrolled cardiac arrhythmia
• No known HIV positivity
• No known hepatitis C virus or acute or chronic active hepatitis B infection
• Adequate oral nutrition

PRIOR CONCURRENT THERAPY:

• More than 21 days since prior laparotomy
• No prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab)
• No prior small molecule EGFR inhibitors (e.g., gefitinib, erlotinib, or lapatinib)
• No prior radiotherapy that would overlap with planned radiotherapy fields
• No prior or other concurrent chemotherapy
• No prior or other concurrent biologic therapy
• More than 4 weeks since prior and no concurrent or planned participation in another experimental drug study except studies with specific interventions intended to treat rashes associated with EGFR agents (e.g., N05C4)
• No concurrent enteral hyperalimentation
• No concurrent chronic immunosuppressive agents (e.g., methotrexate, cyclosporine, or corticosteroids)
• No concurrent colony-stimulating factors during the first course of therapy
• No other concurrent immunotherapy or radiotherapy