Stereotactic Radiation Therapy and Combination Chemotherapy in Treating Patients Undergoing Surgery for Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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RATIONALE: Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving stereotactic radiation therapy together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving stereotactic radiation therapy together with combination chemotherapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the clinical response rate in patients undergoing surgery for locally advanced pancreatic cancer treated with stereotactic radiotherapy, gemcitabine hydrochloride, and oxaliplatin. Secondary Determine the toxicity of this regimen in these patients. Determine the time to disease progression in patients treated with this regimen. Determine the time to death in patients treated with this regimen. Determine perioperative morbidity and mortality in patients treated with this regimen. Determine the rate of R0 resections in patients treated with this regimen. Determine the histologic response rate in these patients. OUTLINE: Neoadjuvant therapy: Patients undergo hypofractionated, stereotactic radiotherapy on days 1-5. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 120 minutes on day 2. Treatment with gemcitabine hydrocloride and oxaliplatin repeats every 2 weeks for 3 courses. Surgery: Patients with resectable disease undergo tumor resection. Patients with unresectable disease undergo a second course of neoadjuvant chemoradiotherapy followed by resection. Adjuvant therapy: Beginning 3-4 weeks after surgery, patients receive 3 more courses of chemotherapy as in neoadjuvant therapy. After completion of study treatment, patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Official Title
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Lokal Fortgeschrittenes Pankreas-Karzinom: Stereotaktische Radiotherapie Gefolfgt Von Gemox-Chemotherapie

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: oxaliplatin
* Procedure: adjuvant therapy
* Procedure: neoadjuvant therapy
* Radiation: hypofractionated radiation therapy
* Radiation: stereotactic radiosurgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the pancreas or intrapancreatic bile duct carcinoma Overall view of image morphology and CA19-9 (< 500 U/L) demonstrating pancreatic cancer allowed if histologic/cytologic confirmation is unavailable Locally advanced disease, meeting 1 of the following criteria: Uncertain R0 resectability dependant on relation to portal vein, sinus confluens, superior mesenteric artery, and superior mesenteric vein (e.g., contact with portal vein, superior mesenteric vein, or arterial vessels, but < 180° encasement) Unresectable pancreatic cancer (e.g., contact with portal vein, superior mesenteric artery or arterial vessels, > 180° encasement) Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 1 cm by spiral CT scan or MRI Patients with no measurable disease may be assessed for feasibility only No distant metastases PATIENT CHARACTERISTICS: ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100% WBC ≥ 3,000/mm³ Granulocyte count ≥ 2,000/mm³ Platelet count ≥ 100,000/mm³ Creatinine clearance > 30 mL/min Bilirubin ≤ 3.0 times upper limit of normal AST and ALT ≤ 2.5 times normal Alkaline phosphatase ≤ 2.5 times normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No secondary malignancy within the past 5 years that was not curatively treated No known intolerance to any of the study drugs No preexisting polyneuropathy > grade 1 No active uncontrolled infection No cardiac insufficiency despite optimal medication No New York Heart Association class III or IV congestive heart failure LVEF ≥ 50% OR shortening fraction ≥ 25% No angina pectoris (at rest or under stress) unexplained by interventional cardiology within the past 6 months No myocardial infarction within the past 6 months No uncontrolled diabetes mellitus No other existing serious medical impairments that would preclude study compliance PRIOR CONCURRENT THERAPY: No prior chemotherapy No prior radiotherapy to the abdomen

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|nan|
|Drug: oxaliplatin|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: neoadjuvant therapy|nan|
|Radiation: hypofractionated radiation therapy|nan|
|Radiation: stereotactic radiosurgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response rate as assessed by RECIST criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by NCI-CTC criteria |  |  | 
| Time to progression |  |  | 
| Time to death |  |  | 
| Perioperative morbidity and mortality |  |  | 
| Rate of R0 resections |  |  | 
| Histologic response rate |  |  | 

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