Radiotherapy Combined With Oxaliplatin and Fluorouracil Followed By Gemcitabine in Treating Patients With Locally Advanced, Unresectable Pancreatic Cancer

• Survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 3 years ]
  The distribution of survival time will be estimated using the method of Kaplan-Meier.
• Confirmed tumor response, defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart [ Time Frame: Up to 6 months ]
• Time to disease progression [ Time Frame: Time from registration to documentation of disease progression, assessed up to 3 years ]
  The distribution of time to progression will be estimated using the method of Kaplan-Meier.
• Duration of response [ Time Frame: Date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 3 years ]
• Time to treatment failure [ Time Frame: Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 3 years ]

PRIMARY OBJECTIVES:

I. Determine the 1-year survival rate in patients with locally advanced, unresectable adenocarcinoma of the pancreas treated with concurrent external beam radiotherapy, oxaliplatin, and fluorouracil followed by gemcitabine.

SECONDARY OBJECTIVES:

I. Determine overall survival, time to disease progression, and confirmed response rate in patients treated with this regimen.

II. Determine toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients undergo radiotherapy once daily, 5 days a week, for 5.5 weeks. Beginning concurrently with radiotherapy, patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and fluorouracil IV continuously for 5.5 weeks. Beginning 4-6 weeks after the completion of chemoradiotherapy, patients receive gemcitabine IV over 30 minutes on days 1 and 8. Treatment with gemcitabine repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

• Adenocarcinoma of the Pancreas
• Stage II Pancreatic Cancer
• Stage III Pancreatic Cancer

• Radiation: radiation therapy
  Undergo radiation therapy
  Other Names:

  • irradiation
  • radiotherapy
  • therapy, radiation
• Drug: oxaliplatin
  Given IV
  Other Names:

  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
• Drug: fluorouracil
  Given IV
  Other Names:

  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
• Drug: gemcitabine hydrochloride
  Given IV
  Other Names:

  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the pancreas

  • Unresectable disease, including subtotal resection and gross residual disease
  • Locally advanced disease
• No cystadenocarcinoma of the pancreas
• No pancreatic tumors of neuroendocrine origin
• No microscopic residual disease as only evidence of pancreatic cancer
• All disease must be encompassable within standard radiotherapy fields for pancreatic cancer

• No distant metastases (liver or lung metastases or peritoneal spread)

  • No evidence of metastatic disease outside the planned radiotherapy field
• Performance status - ECOG 0-1
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 3 times ULN
• Creatinine ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to maintain adequate oral nutrition
• No significant infection
• No significant nausea or vomiting
• No other medical condition that would preclude study participation
• No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or organ-confined prostate cancer (Gleason score < 7)
• No known allergy to platinum compounds
• No prior biologic therapy
• No concurrent biologic therapy
• No concurrent immunotherapy
• No prior chemotherapy
• No other concurrent chemotherapy
• No prior radiotherapy that would overlap planned radiotherapy fields
• No other concurrent radiotherapy
• See Disease Characteristics
• At least 21 days since prior laparotomy