Chemoradiation With Oxaliplatin and Fluorouracil (5FU) for Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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The intention of this trial is to determine the maximum tolerated of the treatment combination and to evaluate its safety and efficacy.

Detailed Description
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Previous studies have demonstrated that neoadjuvant chemoradiation can lead to improved survival with a portion of patients proceeding to resection. This trial will incorporate a similar trial structure using newer agents in patients who present with locally advanced unresectable pancreatic cancer. Specifically oxaliplatin will be used owing to its greater activity in comparison to cisplatin and favorable therapeutic index in combination with radiation compared to gemcitabine. In summary, the primary outcome measure of the phase I portion of the trial is to determine the maximum tolerated dose of this combination. Following the determination of this dose, the phase II portion of the trial will characterize the toxicity of this regimen as well as evaluate for long-term efficacy.

Official Title
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A Phase I/II Study of Chemoradiation With Oxaliplatin and 5FU for Locally Advanced Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: 5FU
* Radiation: Radiation
* Procedure: Surgery
* Drug: FOLFOX 6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented pancreatic adenocarcinoma deemed unresectable due to local involvement of vessels or organs Patients with a clear clinical diagnosis of localized pancreatic cancer deemed unresectable, who have undergone at least 2 biopsies which were not diagnostic of adenocarcinoma, may be entered at the discretion of the principal investigator. No prior chemotherapy or abdominal radiation therapy. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Clinically measurable or evaluable disease. Life expectancy of at least 12 weeks. Adequate bone marrow reserve, granulocyte count >= 1500/uL, platelet count >= 100,000/uL, hemoglobin >= 9 g/dL. Adequate renal function with creatinine =< 1.5 times upper limit of normal (ULN) Adequate biliary function with bilirubin < 3.0 g/dL (including patients who have been bypassed or treated with percutaneous drainage), serum glutamic pyruvic transaminase (SGPT) (alanine transaminase) =< 2.5 Age > 18 years Signed informed consent. No known allergy to one of the study drugs For female patient of childbearing potential, neither pregnant nor breastfeeding, and under active contraception No prior malignancy within last 5 years No central nervous system metastases No peripheral neuropathy > grade2 No other serious concomitant illness Exclusion Criteria: Active infection or uncontrolled infection Presence of metastatic disease. Inadequate organ function as discussed above. Pregnancy Serious concomitant systemic disorder. Use of any investigational agent within a month of treatment

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: Oxaliplatin+ 5FU+ radiation (RT) /surgery /FOLFOX 6<br>Concurrent chemoradiation before surgery and FOLFOX6 regimen after surgery Radiation (RT) 180cGy daily x 5 days/week x 5 weeks, then additional 540 cGy in 3 fractions over a half week to pancreatic portal; Combined with : 5FU 200 mg/m^2 daily by continuous intravenous infusion (CIV) x 5 weeks and weekly Oxaliplatin 60 mg/m^2, IV for 5 weeks (in Phase I, 30, 40, 50, and 60 mg/m^2 Oxaliplatin were tested). Observation for 2 weeks to assess dose-limiting toxicity (DLT)/Response. Surgery if deemed resectable. Then modified FOLFOX 6 for 6 cycles (2 weeks/cycle): Day 1 hour 0: Oxaliplatin 85 mg/m^2 intravenously (IV) + Leucovorin 350 mg IV over 2 hours; hour 2: 5FU 400 mg/m^2 IV bolus followed by 2400 mg/m^2 IV over 46 hours. | Drug: Oxaliplatin<br> <br> * Other names: Oxaliplatin: Eloxatin;Drug: 5FU<br> <br> * Other names: 5-Fluorouracil;Radiation: Radiation<br> <br> Procedure: Surgery<br> <br> Drug: FOLFOX 6<br>* this is an established regimen of Oxaliplatin+infusional 5FU/Leucovorin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resectability After Chemoradiation | This is the number of patients whose tumors are resectable after the combination treatment of 5FU, oxaliplatin, and radiation (RT). | 7.5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Overall Survival | This is the time at which 50% of patients are alive from the trial entry . | up to 10 years since the start of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Locally advanced pancreatic cancer, oxaliplatin, chemoradiation, 5FU