Chemotherapy and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed during surgery. PURPOSE: Randomized phase II trial to compare the effectiveness of two different regimens combining chemotherapy with radiation therapy in treating patients who are undergoing surgery for locally advanced pancreatic cancer.

Detailed Description
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OBJECTIVES: Compare the percentage of margin-free resections in patients with locally advanced, potentially resectable adenocarcinoma of the pancreas treated with gemcitabine and radiotherapy vs gemcitabine, fluorouracil, and cisplatin followed by radiotherapy and fluorouracil. Compare the efficacy of these regimens, as measured by CT scan response, in these patients. Compare the posttreatment fibrosis in resected specimens of patients treated with these regimens. Compare the toxicity of these regimens in these patients. Compare the duration of objective response in patients treated with these regimens. Compare the disease-free and overall survival of patients treated with these regimens. Compare the effect of these regimens and disease recurrence on CA 19-9 values in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to superior mesenteric vein (SMV)/portal vein (PV) occlusion (yes vs no), SMV/PV/superior mesenteric artery/hepatic artery abutment or narrowing (yes vs no), prior exploration (yes vs no), and whether deemed to require preoperative therapy due to other factors (yes vs no). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy once daily 5 days a week for 6 weeks. Patients receive gemcitabine IV over 50 minutes once weekly for 6 weeks during radiotherapy. Patients undergo surgical resection 4-6 weeks after completion of chemoradiotherapy. Maintenance therapy (4-8 weeks after completion of surgery): Patients receive gemcitabine IV over 100 minutes once weekly for 2 weeks. Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients receive gemcitabine IV over 30 minutes on days 1, 5, 29, and 33; cisplatin IV over 60 minutes on days 1-5 and 29-33; and fluorouracil IV continuously on days 1-4 and 29-32. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily on days 6-15 and 34-43 and epoetin alfa SC weekly on weeks 1-9. After completion of chemotherapy, patients undergo radiotherapy once daily 5 days a week for 6 weeks. Patients receive fluorouracil IV continuously daily during radiotherapy. Patients undergo surgical resection 4-6 weeks after completion of chemoradiotherapy. Maintenance therapy (4-8 weeks after completion of surgery): Patients receive gemcitabine IV over 100 minutes once weekly for 2 weeks. Treatment repeats every 3 weeks for 3 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 2 years. PROJECTED ACCRUAL: A total of 80-160 patients (40-80 per treatment arm) will be accrued for this study.

Official Title
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A Randomized Phase II Study Of Gemcitabine Plus Radiotherapy Vs. Gemcitabine, 5-Fluorouracil And Cisplatin Followed By Radiotherapy And 5-Fluoraracil For Patients With Locally Advanced, Potentially Resectable Pancreatic Adenocarcinoma

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Biological: epoetin alfa
* Biological: filgrastim
* Drug: cisplatin
* Drug: fluorouracil
* Drug: gemcitabine hydrochloride
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the pancreas No adenosquamous cancers or adenocarcinoma associated with cystic mucinous neoplasms Locally advanced disease that is potentially resectable, previously explored and considered unresectable, or deemed to require preoperative treatment for other reasons Primary cancer in the head, body, or tail of pancreas Measurable disease No 360 degree encirclement of the superior mesenteric artery, hepatic artery, or celiac axis No metastases by CT scan and laparoscopy (if prior surgery, only CT scan required) PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute granulocyte count greater than 2,000/mm^3 Platelet count greater than 100,000/mm^3 Hepatic Bilirubin less than 2 mg/dL (unless secondary to bile duct blockage by tumor) Biliary obstruction by tumor requires biliary stent at least 9 French or biliary bypass before therapy Renal Creatinine less than 1.7 mg/dL OR Creatinine clearance greater than 60 mL/min Other No other malignancy within the past 3 years except nonmelanoma skin cancer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for this disease Endocrine therapy Not specified Radiotherapy No prior radiotherapy to pancreas Surgery Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: epoetin alfa|nan|
|Biological: filgrastim|nan|
|Drug: cisplatin|nan|
|Drug: fluorouracil|nan|
|Drug: gemcitabine hydrochloride|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: conventional surgery|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of margin-free resections produced by each program |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy as measured by CT scan response |  |  | 
| Post-treatment fibrosis in the resected specimens |  |  | 
| Toxicity |  |  | 
| Duration of objective response |  |  | 
| Disease-free survival |  |  | 
| Overall survival |  |  | 
| Effect of therapy and recurrence on CA19-9 values |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the pancreas, stage II pancreatic cancer, stage III pancreatic cancer