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

Study Overview
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Brief Summary
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This phase II trial is studying how well giving radiation therapy together with oxaliplatin and fluorouracil followed by gemcitabine works in treating patients with locally advanced, unresectable pancreatic cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as oxaliplatin, fluorouracil, and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Oxaliplatin may also make the tumor cells more sensitive to radiation therapy. Giving radiation therapy with chemotherapy may kill more tumor cells.

Detailed Description
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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.

Official Title
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Phase II Study of Oxaliplatin, Continuous 5-Fluorouracil and External Beam Radiation Followed by Gemcitabine in Patients With Locally Advanced Pancreatic Cancer

Conditions
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Adenocarcinoma of the Pancreas, Stage II Pancreatic Cancer, Stage III Pancreatic Cancer

Intervention / Treatment
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* Radiation: radiation therapy
* Drug: oxaliplatin
* Drug: fluorouracil
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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. | Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;Drug: oxaliplatin<br>* Given IV<br>* Other names: L-OHP;Drug: fluorouracil<br>* Given IV<br>* Other names: 5-FU;Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year survival rate | 1-year survival will be considered success. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. If more than 1 patients is lost to follow-up, we will use Kaplan-Meier estimates for the 6-month and 12-month overall survival rates. 95% confidence intervals for the true success proportion will be calculated according the approach of Duffy and Santner. | At 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival time | The distribution of survival time will be estimated using the method of Kaplan-Meier. | Time from registration to death due to any cause, assessed up to 3 years | 
| Confirmed tumor response, defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart |  | Up to 6 months | 
| Time to disease progression | The distribution of time to progression will be estimated using the method of Kaplan-Meier. | Time from registration to documentation of disease progression, assessed up to 3 years | 
| Duration of response |  | 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 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 |