Margin-Intense Combo Therapy in Pts w/Potentially Resectable Pancreatic Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Stereotactic body 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 hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving stereotactic body radiation therapy together with gemcitabine hydrochloride may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of stereotactic body radiation therapy when given with or without gemcitabine hydrochloride in treating patients with pancreatic cancer that can be removed by surgery.

Detailed Description
-----------------
OBJECTIVES: To demonstrate the feasibility and safety of administering margin-intensive stereotactic body radiotherapy together with preoperative gemcitabine hydrochloride to patients with resectable pancreatic adenocarcinoma. OUTLINE: This is a multicenter, dose-escalation study of gemcitabine hydrochloride. Patients receive 1 of 2 treatment regimens. Regimen 1: Patients undergo a single fraction of margin-intensive stereotactic body radiotherapy (SBRT) on day 1. Patients undergo pancreatoduodenectomy between days 15-43. Regimen 2: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients undergo a single fraction of SBRT between days 21-28 followed by pancreatoduodenectomy between days 35-63. After completion of study treatment, patients are followed periodically for 5 years.

Official Title
-----------------
Phase I Study of Margin-Intense Combination Therapy for Patients With Potentially Resectable Pancreatic Adenocarcinoma

Conditions
-----------------
Pancreatic Cancer

Intervention / Treatment
-----------------
* Drug: gemcitabine hydrochloride
* Radiation: stereotactic body radiation therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Pathologically confirmed localized adenocarcinoma of the pancreas or distal common bile duct Pancreatic ductal adenocarcinoma or peripancreatic cholangiocarcinoma Resectable disease, as determined by the Gastrointestinal Cancer Working Group disease-oriented team Criteria used to define unresectability will include, but not be limited to, the following: Tumor encases > 180 degrees of the circumference of the superior mesenteric artery Tumor encases the common hepatic artery with no anatomic option for reconstruction following segmental resection Superior mesenteric vein occluded or encased with no option for reconstruction following segmental resection Soft tissue infiltration of the retroperitoneum to the left of the superior mesenteric artery All malignant disease must be encompassed within a single radiotherapy field No metastatic disease PATIENT CHARACTERISTICS: Zubrod performance status 0-1 Absolute granulocyte count > 1,500/mm³ Platelet count > 100,000/mm³ Creatinine clearance > 50mL/min AST and ALT < 5 times upper limit of normal Serum bilirubin < 5 mg/dL (with biliary decompression) INR ≤ 1.5 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Medically fit for pancreatic surgical resection, as determined by the investigating surgeons at the time of study enrollment No evidence of an active second invasive malignancy outside the area of the pancreas or biliary system within the past 2 years, except for non-melanomatous skin cancer or carcinoma in situ of the breast, bladder, cervix, or uterus No clinically significant cardiac disease, including the following: Uncontrolled hypertension, defined as blood pressure > 160/90 mm Hg on medication Myocardial infarction within the past 6 months NYHA class II-IV congestive heart failure Unstable symptomatic arrhythmia requiring medication (e.g., chronic atrial arrhythmia [atrial fibrillation or paroxysmal supraventricular tachycardia]) Atrial arrhythmia allowed provided it is well-controlled on stable medication No current or recent (within the past 6 months) unstable angina No recent (within the past 6 months) arterial thromboembolic events, including transient ischemic attack, cerebrovascular accident, or clinically significant peripheral artery disease No evidence of bleeding diathesis or coagulopathy No significant traumatic injury within the past 28 days No serious nonhealing wound, ulcer, or currently healing fracture No AIDS No significant infection or other coexisting medical condition that would preclude study therapy No gastrointestinal fistula or perforation within the past 10 years PRIOR CONCURRENT THERAPY: More than 2 years since prior chemotherapy (other than for pancreaticobiliary cancer) More than 28 days since prior major surgical procedure or open biopsy No prior intraabdominal radiotherapy in the planned field of pancreatic margin-intensive radiotherapy No prior organ transplantation No concurrent major surgical procedure No other concurrent cytotoxic chemotherapy or anti-neoplastic biologic agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen 1<br>Patients undergo a single fraction of margin-intensive stereotactic body radiotherapy (SBRT) on day 1. Patients undergo pancreatoduodenectomy between days 15-43. | Radiation: stereotactic body radiation therapy<br>* Given as a single fraction<br>|
| Experimental: Regimen 2<br>Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, and 15. Patients undergo a single fraction of SBRT between days 21-28 followed by pancreatoduodenectomy between days 35-63. | Drug: gemcitabine hydrochloride<br>* Given IV<br>Radiation: stereotactic body radiation therapy<br>* Given as a single fraction<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preoperative treatment-related toxicity, defined as adverse events occurring prior to surgical resection |  |  | 
| Postoperative surgical morbidity, defined as all other adverse events occurring within 90 days of surgery |  |  | 
| Total dose of chemotherapy and radiotherapy delivered |  |  | 
| Pre-treatment and post-treatment characteristics of the primary tumor on preoperative axial imaging including, but not limited to, tumor size, percentage of encasement/abutment of mesenteric vessels, and progression of disease |  |  | 
| Postoperative complications including, but not limited to, need for reoperation, need for interventional radiology fluid collection drainage, systemic infection, wound infection, prolonged ICU stay, and delayed gastric emptying |  |  | 
| Operative drain amylase at days 3 and 5 postoperatively |  |  | 
| Length of hospital stay following pancreatic resection |  |  | 
| Degree of histologic response of tumor in the resected specimen |  |  | 
| Tumor samples for RNA and protein harvesting (when possible) from pretreatment biopsies and surgical specimens |  |  | 

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